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Sample records for nonclassical ran-dependent pathway

  1. Serum ferritin is derived primarily from macrophages through a nonclassical secretory pathway.

    Science.gov (United States)

    Cohen, Lyora A; Gutierrez, Lucia; Weiss, Avital; Leichtmann-Bardoogo, Yael; Zhang, De-liang; Crooks, Daniel R; Sougrat, Rachid; Morgenstern, Avigail; Galy, Bruno; Hentze, Matthias W; Lazaro, Francisco J; Rouault, Tracey A; Meyron-Holtz, Esther G

    2010-09-02

    The serum ferritin concentration is a clinical parameter measured widely for the differential diagnosis of anemia. Its levels increase with elevations of tissue iron stores and with inflammation, but studies on cellular sources of serum ferritin as well as its subunit composition, degree of iron loading and glycosylation have given rise to conflicting results. To gain further understanding of serum ferritin, we have used traditional and modern methodologies to characterize mouse serum ferritin. We find that both splenic macrophages and proximal tubule cells of the kidney are possible cellular sources for serum ferritin and that serum ferritin is secreted by cells rather than being the product of a cytosolic leak from damaged cells. Mouse serum ferritin is composed mostly of L-subunits, whereas it contains few H-subunits and iron content is low. L-subunits of serum ferritin are frequently truncated at the C-terminus, giving rise to a characteristic 17-kD band that has been previously observed in lysosomal ferritin. Taken together with the fact that mouse serum ferritin is not detectably glycosylated, we propose that mouse serum ferritin is secreted through the nonclassical lysosomal secretory pathway.

  2. A non-classical assembly pathway of Escherichia coli pore-forming toxin cytolysin A.

    Science.gov (United States)

    Fahie, Monifa; Romano, Fabian B; Chisholm, Christina; Heuck, Alejandro P; Zbinden, Mark; Chen, Min

    2013-10-25

    Cytolysin A (ClyA) is an α-pore forming toxin from pathogenic Escherichia coli (E. coli) and Salmonella enterica. Here, we report that E. coli ClyA assembles into an oligomeric structure in solution in the absence of either bilayer membranes or detergents at physiological temperature. These oligomers can rearrange to create transmembrane pores when in contact with detergents or biological membranes. Intrinsic fluorescence measurements revealed that oligomers adopted an intermediate state found during the transition between monomer and transmembrane pore. These results indicate that the water-soluble oligomer represents a prepore intermediate state. Furthermore, we show that ClyA does not form transmembrane pores on E. coli lipid membranes. Because ClyA is delivered to the target host cell in an oligomeric conformation within outer membrane vesicles (OMVs), our findings suggest ClyA forms a prepore oligomeric structure independently of the lipid membrane within the OMV. The proposed model for ClyA represents a non-classical pathway to attack eukaryotic host cells.

  3. Bisphenol-A acts as a potent estrogen via non-classical estrogen triggered pathways.

    Science.gov (United States)

    Alonso-Magdalena, Paloma; Ropero, Ana Belén; Soriano, Sergi; García-Arévalo, Marta; Ripoll, Cristina; Fuentes, Esther; Quesada, Iván; Nadal, Ángel

    2012-05-22

    Bisphenol-A (BPA) is an estrogenic monomer commonly used in the manufacture of numerous consumer products such as food and beverage containers. Widespread human exposure to significant doses of this compound has been reported. Traditionally, BPA has been considered a weak estrogen, based on its lower binding affinity to the nuclear estrogen receptors (ERs) compared to 17-β estradiol (E2) as well as its low transcriptional activity after ERs activation. However, in vivo animal studies have demonstrated that it can interfere with endocrine signaling pathways at low doses during fetal, neonatal or perinatal periods as well as in adulthood. In addition, mounting evidence suggests a variety of pathways through which BPA can elicit cellular responses at very low concentrations with the same or even higher efficiency than E2. Thus, the purpose of the present review is to analyze with substantiated scientific evidence the strong estrogenic activity of BPA when it acts through alternative mechanisms of action at least in certain cell types.

  4. In Vitro Characterization of the Two-Stage Non-Classical Reassembly Pathway of S-Layers

    Science.gov (United States)

    Breitwieser, Andreas; Iturri, Jagoba; Toca-Herrera, Jose-Luis; Sleytr, Uwe B.; Pum, Dietmar

    2017-01-01

    The recombinant bacterial surface layer (S-layer) protein rSbpA of Lysinibacillus sphaericus CCM 2177 is an ideal model system to study non-classical nucleation and growth of protein crystals at surfaces since the recrystallization process may be separated into two distinct steps: (i) adsorption of S-layer protein monomers on silicon surfaces is completed within 5 min and the amount of bound S-layer protein sufficient for the subsequent formation of a closed crystalline monolayer; (ii) the recrystallization process is triggered—after washing away the unbound S-layer protein—by the addition of a CaCl2 containing buffer solution, and completed after approximately 2 h. The entire self-assembly process including the formation of amorphous clusters, the subsequent transformation into crystalline monomolecular arrays, and finally crystal growth into extended lattices was investigated by quartz crystal microbalance with dissipation (QCM-D) and atomic force microscopy (AFM). Moreover, contact angle measurements showed that the surface properties of S-layers change from hydrophilic to hydrophobic as the crystallization proceeds. This two-step approach is new in basic and application driven S-layer research and, most likely, will have advantages for functionalizing surfaces (e.g., by spray-coating) with tailor-made biological sensing layers. PMID:28216572

  5. In Vitro Characterization of the Two-Stage Non-Classical Reassembly Pathway of S-Layers

    Directory of Open Access Journals (Sweden)

    Andreas Breitwieser

    2017-02-01

    Full Text Available The recombinant bacterial surface layer (S-layer protein rSbpA of Lysinibacillus sphaericus CCM 2177 is an ideal model system to study non-classical nucleation and growth of protein crystals at surfaces since the recrystallization process may be separated into two distinct steps: (i adsorption of S-layer protein monomers on silicon surfaces is completed within 5 min and the amount of bound S-layer protein sufficient for the subsequent formation of a closed crystalline monolayer; (ii the recrystallization process is triggered—after washing away the unbound S-layer protein—by the addition of a CaCl2 containing buffer solution, and completed after approximately 2 h. The entire self-assembly process including the formation of amorphous clusters, the subsequent transformation into crystalline monomolecular arrays, and finally crystal growth into extended lattices was investigated by quartz crystal microbalance with dissipation (QCM-D and atomic force microscopy (AFM. Moreover, contact angle measurements showed that the surface properties of S-layers change from hydrophilic to hydrophobic as the crystallization proceeds. This two-step approach is new in basic and application driven S-layer research and, most likely, will have advantages for functionalizing surfaces (e.g., by spray-coating with tailor-made biological sensing layers.

  6. Quantification of nonclassicality

    Energy Technology Data Exchange (ETDEWEB)

    Mraz, Melanie; Sperling, Jan; Vogel, Werner; Hage, Boris [Universitaet Rostock, Institut fuer Physik, Rostock (Germany)

    2013-07-01

    At the beginning of the 20th century the discussion on physics beyond the classical regime started. This was the hour of birth of quantum physics and, with Einstein's description of the photoelectric effect, of quantum optics. Even the physicists had problems to understand nonclassical quantum phenomena, because of its non-intuitive properties. So, why further struggling? Nonclassical states have an advantage over classical states for various applications. Only one example is the quantum teleportation which would be unthinkable without nonclassical states. Hence, it is of a fundamental interest to study properties of nonclassical quantum states. It is already possible to say if a state is nonclassical or not, but how can we decide how much nonclassicality is in our system? We propose a degree of nonclassicality being a nonclassicality measure. It is determined by the decomposition of a quantum state into superpositions of coherent states. On the one hand, coherent states resembles the behavior of a classical harmonic oscillator most closely. On the other hand, the more quantum superpositions of coherent states are needed, the more quantum interferences arise. A method for such a decomposition of quantum states is presented and the degree of nonclassicality is determined for different states. We apply our method to typical nonclassical states, such as the compass state and the squeezed vacuum state.

  7. Conservation of complex nuclear localization signals utilizing classical and non-classical nuclear import pathways in LANA homologs of KSHV and RFHV.

    Directory of Open Access Journals (Sweden)

    Lidia Cherezova

    Full Text Available ORF73 latency-associated nuclear antigen (LANA of the Kaposi's sarcoma-associated herpesvirus (KSHV is targeted to the nucleus of infected cells where it binds to chromatin and mediates viral episome persistence, interacts with cellular proteins and plays a role in latency and tumorigenesis. A structurally related LANA homolog has been identified in the retroperitoneal fibromatosis herpesvirus (RFHV, the macaque homolog of KSHV. Here, we report the evolutionary and functional conservation of a novel bi-functional nuclear localization signal (NLS in KSHV and RFHV LANA. N-terminal peptides from both proteins were fused to EGFP or double EGFP fusions to examine their ability to induce nuclear transport of a heterologous protein. In addition, GST-pull down experiments were used to analyze the ability of LANA peptides to interact with members of the karyopherin family of nuclear transport receptors. Our studies revealed that both LANA proteins contain an N-terminal arginine/glycine (RG-rich domain spanning a conserved chromatin-binding motif, which binds directly to importin β1 in a RanGTP-sensitive manner and serves as an NLS in the importin β1-mediated non-classical nuclear import pathway. Embedded within this domain is a conserved lysine/arginine-(KR-rich bipartite motif that binds directly to multiple members of the importin α family of nuclear import adaptors in a RanGTP-insensitive manner and serves as an NLS in the classical importin α/β-mediated nuclear import pathway. The positioning of a classical bipartite kr-NLS embedded within a non-classical rg-NLS is a unique arrangement in these viral proteins, whose nuclear localization is critical to their functionality and to the virus life cycle. The ability to interact with multiple import receptors provides alternate pathways for nuclear localization of LANA. Since different import receptors can import cargo to distinct subnuclear compartments, a multifunctional NLS may provide LANA with an

  8. S100A13-C2A binary complex structure-a key component in the acidic fibroblast growth factor for the non-classical pathway.

    Science.gov (United States)

    Mohan, Sepuru K; Rani, Sandhya G; Kumar, Sriramoju M; Yu, Chin

    2009-03-13

    Fibroblast growth factors (FGFs) are key regulators of cell proliferation, differentiation, tumor-induced angiogenesis and migration. FGFs are essential for early embryonic development, organ formation and angiogenesis. They play important roles in tumor formation, inflammation, wound healing and restenosis. The biological effects of FGFs are mediated through the activation of the four transmembrane phosphotyrosine kinase receptors (FGFRs) in the presence of heparin sulfate proteoglycans (HSPGs) and therefore require the release of FGFs into the extracellular space. However, FGF-1 lacks the signal peptide required for the releasing of these proteins through the classical endoplasmic reticulum (ER)-Golgi secretary pathway. Maciag et al. demonstrated that FGF-1 is exported through a non-classical release pathway involving the formation of a specific multiprotein complex [M. Landriscina, R. Soldi, C. Bagala, I. Micucci, S. Bellum, F. Tarantini, I. Prudovsky, T. Maciag, S100A13 participates in the release of fibroblast growth factor 1 in response to heat shock in vitro, J. Biol. Chem. 276 (2001) 22544-22552; C.M. Carreira, T.M. LaVallee, F. Tarantini, A. Jackson, J.T. Lathrop, B. Hampton, W.H. Burgess, T. Maciag, S100A13 is involved in the regulation of fibroblast growth factor-1 and p40 synaptotagmin-1 release in vitro, J. Biol. Chem. 273 (1998) 22224-22231; T.M. LaValle, F. Tarantini, S. Gamble, C.M. Carreira, A. Jackson, T. Maciag, Synaptotagmin-1 is required for fibroblast growth factor-1 release, J. Biol. Chem. 273 (1998) 22217-22223; C. Bagalá, V. Kolev, A. Mandinova, R. Soldi, C. Mouta, I. Graziani, I, Prudovsky, T. Maciag, The alternative translation of synaptotagmin 1 mediates the non-classical release of FGF1, Biochem. Biophys. Res. Commun. 310 (2003) 1041-1047]. The protein constituents of this complex include FGF-1, S100A13 (a Ca(2+)-binding protein), and the p40 form of synaptotagmin 1 (Syt1). To understand the molecular events in the FGF-1 releasing

  9. Conditional Hybrid Nonclassicality

    Science.gov (United States)

    Agudelo, E.; Sperling, J.; Costanzo, L. S.; Bellini, M.; Zavatta, A.; Vogel, W.

    2017-09-01

    We derive and implement a general method to characterize the nonclassicality in compound discrete- and continuous-variable systems. For this purpose, we introduce the operational notion of conditional hybrid nonclassicality which relates to the ability to produce a nonclassical continuous-variable state by projecting onto a general superposition of discrete-variable subsystem. We discuss the importance of this form of quantumness in connection with interfaces for quantum communication. To verify the conditional hybrid nonclassicality, a matrix version of a nonclassicality quasiprobability is derived and its sampling approach is formulated. We experimentally generate an entangled, hybrid Schrödinger cat state, using a coherent photon-addition process acting on two temporal modes, and we directly sample its nonclassicality quasiprobability matrix. The introduced conditional quantum effects are certified with high statistical significance.

  10. Non-classical antigen processing pathways are required for MHC class II-restricted direct tumor recognition by NY-ESO-1-specific CD4+ T cells

    Science.gov (United States)

    Matsuzaki, Junko; Tsuji, Takemasa; Luescher, Immanuel; Old, Lloyd J.; Shrikant, Protul; Gnjatic, Sacha; Odunsi, Kunle

    2014-01-01

    Tumor antigen-specific CD4+ T cells that directly recognize cancer cells are important for orchestrating antitumor immune responses at the local tumor sites. However, the mechanisms of direct MHC class II (MHC-II) presentation of intracellular tumor antigen by cancer cells are poorly understood. We found that two functionally distinct subsets of CD4+ T cells were expanded after HLA-DPB1*04 (DP04)-binding NY-ESO-1157–170 peptide vaccination in ovarian cancer patients. While both subsets similarly recognized exogenous NY-ESO-1 protein pulsed on DP04+ target cells, only one type recognized target cells with intracellular expression of NY-ESO-1. The tumor-recognizing CD4+ T cells more efficiently recognized the short 8–9-mer peptides than the non-tumor-recognizing CD4+ T cells. In addition to endosomal/lysosomal proteases that are typically involved in MHC-II antigen presentation, several pathways in the MHC class I presentation pathways such as the proteasomal degradation and transporter-associated with antigen-processing (TAP)-mediated peptide transport were also involved in the presentation of intracellular NY-ESO-1 on MHC-II. The presentation was inhibited significantly by primaquine, a small molecule that inhibits endosomal recycling, consistent with findings that pharmacological inhibition of new protein synthesis enhances antigen presentation. Together, our data demonstrated that cancer cells selectively present peptides from intracellular tumor antigens on MHC-II by multiple non-classical antigen-processing pathways. Harnessing direct tumor-recognizing ability of CD4+ T cells could be a promising strategy to enhance antitumor immune responses in the immunosuppressive tumor microenvironment. PMID:24764581

  11. Nonclassical antigen-processing pathways are required for MHC class II-restricted direct tumor recognition by NY-ESO-1-specific CD4(+) T cells.

    Science.gov (United States)

    Matsuzaki, Junko; Tsuji, Takemasa; Luescher, Immanuel; Old, Lloyd J; Shrikant, Protul; Gnjatic, Sacha; Odunsi, Kunle

    2014-04-01

    Tumor antigen-specific CD4(+) T cells that directly recognize cancer cells are important for orchestrating antitumor immune responses at the local tumor sites. However, the mechanisms of direct MHC class II (MHC-II) presentation of intracellular tumor antigen by cancer cells are poorly understood. We found that two functionally distinct subsets of CD4(+) T cells were expanded after HLA-DPB1*04 (DP04)-binding NY-ESO-1157-170 peptide vaccination in patients with ovarian cancer. Although both subsets recognized exogenous NY-ESO-1 protein pulsed on DP04(+) target cells, only one type recognized target cells with intracellular expression of NY-ESO-1. The tumor-recognizing CD4(+) T cells more efficiently recognized the short 8-9-mer peptides than the non-tumor-recognizing CD4(+) T cells. In addition to endosomal/lysosomal proteases that are typically involved in MHC-II antigen presentation, several pathways in the MHC class I presentation pathways, such as the proteasomal degradation and transporter-associated with antigen-processing-mediated peptide transport, were also involved in the presentation of intracellular NY-ESO-1 on MHC-II. The presentation was inhibited significantly by primaquine, a small molecule that inhibits endosomal recycling, consistent with findings that pharmacologic inhibition of new protein synthesis enhances antigen presentation. Together, our data demonstrate that cancer cells selectively present peptides from intracellular tumor antigens on MHC-II by multiple nonclassical antigen-processing pathways. Harnessing the direct tumor-recognizing ability of CD4(+) T cells could be a promising strategy to enhance antitumor immune responses in the immunosuppressive tumor microenvironment.

  12. Converting Nonclassicality into Entanglement

    Science.gov (United States)

    Killoran, N.; Steinhoff, F. E. S.; Plenio, M. B.

    2016-02-01

    Quantum mechanics exhibits a wide range of nonclassical features, of which entanglement in multipartite systems takes a central place. In several specific settings, it is well known that nonclassicality (e.g., squeezing, spin squeezing, coherence) can be converted into entanglement. In this work, we present a general framework, based on superposition, for structurally connecting and converting nonclassicality to entanglement. In addition to capturing the previously known results, this framework also allows us to uncover new entanglement convertibility theorems in two broad scenarios, one which is discrete and one which is continuous. In the discrete setting, the classical states can be any finite linearly independent set. For the continuous setting, the pertinent classical states are "symmetric coherent states," connected with symmetric representations of the group S U (K ). These results generalize and link convertibility properties from the resource theory of coherence, spin coherent states, and optical coherent states, while also revealing important connections between local and nonlocal pictures of nonclassicality.

  13. Converting Nonclassicality into Entanglement.

    Science.gov (United States)

    Killoran, N; Steinhoff, F E S; Plenio, M B

    2016-02-26

    Quantum mechanics exhibits a wide range of nonclassical features, of which entanglement in multipartite systems takes a central place. In several specific settings, it is well known that nonclassicality (e.g., squeezing, spin squeezing, coherence) can be converted into entanglement. In this work, we present a general framework, based on superposition, for structurally connecting and converting nonclassicality to entanglement. In addition to capturing the previously known results, this framework also allows us to uncover new entanglement convertibility theorems in two broad scenarios, one which is discrete and one which is continuous. In the discrete setting, the classical states can be any finite linearly independent set. For the continuous setting, the pertinent classical states are "symmetric coherent states," connected with symmetric representations of the group SU(K). These results generalize and link convertibility properties from the resource theory of coherence, spin coherent states, and optical coherent states, while also revealing important connections between local and nonlocal pictures of nonclassicality.

  14. Non-classical protein secretion in bacteria

    Directory of Open Access Journals (Sweden)

    Fausbøll Anders

    2005-10-01

    Full Text Available Abstract Background We present an overview of bacterial non-classical secretion and a prediction method for identification of proteins following signal peptide independent secretion pathways. We have compiled a list of proteins found extracellularly despite the absence of a signal peptide. Some of these proteins also have known roles in the cytoplasm, which means they could be so-called "moon-lightning" proteins having more than one function. Results A thorough literature search was conducted to compile a list of currently known bacterial non-classically secreted proteins. Pattern finding methods were applied to the sequences in order to identify putative signal sequences or motifs responsible for their secretion. We have found no signal or motif characteristic to any majority of the proteins in the compiled list of non-classically secreted proteins, and conclude that these proteins, indeed, seem to be secreted in a novel fashion. However, we also show that the apparently non-classically secreted proteins are still distinguished from cellular proteins by properties such as amino acid composition, secondary structure and disordered regions. Specifically, prediction of disorder reveals that bacterial secretory proteins are more structurally disordered than their cytoplasmic counterparts. Finally, artificial neural networks were used to construct protein feature based methods for identification of non-classically secreted proteins in both Gram-positive and Gram-negative bacteria. Conclusion We present a publicly available prediction method capable of discriminating between this group of proteins and other proteins, thus allowing for the identification of novel non-classically secreted proteins. We suggest candidates for non-classically secreted proteins in Escherichia coli and Bacillus subtilis. The prediction method is available online.

  15. Tomography of nonclassical states

    NARCIS (Netherlands)

    Bazrafkan, MR; Man'ko, [No Value

    2003-01-01

    A review of the symplectic tomography method is presented. Superpositions of different types of photon states are considered within the framework of the tomography approach. Such nonclassical photon states as even and odd coherent states, crystallized Schrodinger cat states, and other superposition

  16. Tomography of nonclassical states

    NARCIS (Netherlands)

    Bazrafkan, MR; Man'ko, [No Value

    2003-01-01

    A review of the symplectic tomography method is presented. Superpositions of different types of photon states are considered within the framework of the tomography approach. Such nonclassical photon states as even and odd coherent states, crystallized Schrodinger cat states, and other superposition

  17. Mouse Spermatogenesis Requires Classical and Nonclassical Testosterone Signaling.

    Science.gov (United States)

    Toocheck, Corey; Clister, Terri; Shupe, John; Crum, Chelsea; Ravindranathan, Preethi; Lee, Tae-Kyung; Ahn, Jung-Mo; Raj, Ganesh V; Sukhwani, Meena; Orwig, Kyle E; Walker, William H

    2016-01-01

    Testosterone acts though the androgen receptor in Sertoli cells to support germ cell development (spermatogenesis) and male fertility, but the molecular and cellular mechanisms by which testosterone acts are not well understood. Previously, we found that in addition to acting through androgen receptor to directly regulate gene expression (classical testosterone signaling pathway), testosterone acts through a nonclassical pathway via the androgen receptor to rapidly activate kinases that are known to regulate spermatogenesis. In this study, we provide the first evidence that nonclassical testosterone signaling occurs in vivo as the MAP kinase cascade is rapidly activated in Sertoli cells within the testis by increasing testosterone levels in the rat. We find that either classical or nonclassical signaling regulates testosterone-mediated Rhox5 gene expression in Sertoli cells within testis explants. The selective activation of classical or nonclassical signaling pathways in Sertoli cells within testis explants also resulted in the differential activation of the Zbtb16 and c-Kit genes in adjacent spermatogonia germ cells. Delivery of an inhibitor of either pathway to Sertoli cells of mouse testes disrupted the blood-testis barrier that is essential for spermatogenesis. Furthermore, an inhibitor of nonclassical testosterone signaling blocked meiosis in pubertal mice and caused the loss of meiotic and postmeiotic germ cells in adult mouse testes. An inhibitor of the classical pathway caused the premature release of immature germ cells. Collectively, these observations indicate that classical and nonclassical testosterone signaling regulate overlapping and distinct functions that are required for the maintenance of spermatogenesis and male fertility.

  18. Nonclassic Congenital Adrenal Hyperplasia

    Directory of Open Access Journals (Sweden)

    Selma Feldman Witchel

    2010-01-01

    Full Text Available Nonclassic congenital adrenal hyperplasia (NCAH due to P450c21 (21-hydroxylase deficiency is a common autosomal recessive disorder. This disorder is due to mutations in the CYP21A2 gene which is located at chromosome 6p21. The clinical features predominantly reflect androgen excess rather than adrenal insufficiency leading to an ascertainment bias favoring diagnosis in females. Treatment goals include normal linear growth velocity and “on-time” puberty in affected children. For adolescent and adult women, treatment goals include regularization of menses, prevention of progression of hirsutism, and fertility. This paper will review key aspects regarding pathophysiology, diagnosis, and treatment of NCAH.

  19. Nonclassicality of noisy quantum states

    CERN Document Server

    Semenov, A A; Vasylyev, D Y

    2005-01-01

    Nonclassicality conditions for an oscillator-like system interacting with a hot thermal bath are considered. Nonclassical properties of quantum states can be conserved up to a certain temperature threshold only. In this case affection of the thermal noise can be compensated via transformation of an observable, which tests the nonclassicality (witness function). Possibilities for experimental implementations based on unbalanced homodyning are discussed. At the same time we demonstrate that the scheme based on balanced homodyning cannot be improved for noisy states with proposed technique and should be applied directly.

  20. The Nonclassical Diffusion Approximation to the Nonclassical Linear Boltzmann Equation

    CERN Document Server

    Vasques, Richard

    2015-01-01

    We show that, by correctly selecting the probability distribution function $p(s)$ for a particle's distance-to-collision, the nonclassical diffusion equation can be represented exactly by the nonclassical linear Boltzmann equation for an infinite homogeneous medium. This choice of $p(s)$ preserves the $true$ mean-squared free path of the system, which sheds new light on the results obtained in previous work.

  1. Geniposide, the component of the Chinese herbal formula Tongluojiunao, protects amyloid-βpeptide (1-42)-mediated death of hippocampal neurons via the non-classical estrogen signaling pathway

    Institute of Scientific and Technical Information of China (English)

    Jiao Li; Yan Tan; Qi Zhang; Xu Wang; Angran Fan; Qian Hua; Feng Wang; Haimin Ding; Chunyan Jin; Jinyan Chen; Yanan Zhao; Xiaojing Li; Wenju Chen; Ping Sun

    2014-01-01

    Tongluojiunao (TLJN) is an herbal medicine consisting of two main components, geniposide and ginsenoside Rg1. TLJN has been shown to protect primary cultured hippocampal neurons. How-ever, its mechanism of action remains unclear. In the present study, primary cultured hippocampal neurons treated with Aβ1-42 (10 µmol/L) signiifcantly increased the release of lactate dehydroge-nase, which was markedly reduced by TLJN (2 µL/mL), speciifcally by the component geniposide (26 µmol/L), but not ginsenoside Rg1 (2.5 µmol/L). hTe estrogen receptor inhibitor, ICI182780 (1 µmol/L), did not block TLJN-or geniposide-mediated decrease of lactate dehydrogenase under Aβ1-42-exposed conditions. However, the phosphatidyl inositol 3-kinase or mitogen-activated protein kinase pathway inhibitor, LY294002 (50 µmol/L) or U0126 (10 µmol/L), respectively blo cked the decrease of lactate dehydrogenase mediated by TLJN or geniposide. hTerefore, these results suggest that the non-classical estrogen pathway (i.e., phosphatidyl inositol 3-kinase or mitogen-activated protein kinase) is involved in the neuroprotective effect of TLJN, speciifcally its component, geniposide, against Aβ1-42-mediated cell death in primary cultured hippocampal neurons.

  2. Phonon-Mediated Nonclassical Interference in Diamond

    Science.gov (United States)

    England, Duncan G.; Fisher, Kent A. G.; MacLean, Jean-Philippe W.; Bustard, Philip J.; Heshami, Khabat; Resch, Kevin J.; Sussman, Benjamin J.

    2016-08-01

    Quantum interference of single photons is a fundamental aspect of many photonic quantum processing and communication protocols. Interference requires that the multiple pathways through an interferometer be temporally indistinguishable to within the coherence time of the photon. In this Letter, we use a diamond quantum memory to demonstrate interference between quantum pathways, initially temporally separated by many multiples of the optical coherence time. The quantum memory can be viewed as a light-matter beam splitter, mapping a THz-bandwidth single photon to a variable superposition of the output optical mode and stored phononic mode. Because the memory acts both as a beam splitter and as a buffer, the relevant coherence time for interference is not that of the photon, but rather that of the memory. We use this mechanism to demonstrate nonclassical single-photon and two-photon interference between quantum pathways initially separated by several picoseconds, even though the duration of the photons themselves is just ˜250 fs .

  3. Nonlinearity and nonclassicality in a nanomechanical resonator

    Energy Technology Data Exchange (ETDEWEB)

    Teklu, Berihu [Clermont Universite, Blaise Pascal University, CNRS, PHOTON-N2, Institut Pascal, Aubiere Cedex (France); Universita degli Studi di Milano, Dipartimento di Fisica, Milano (Italy); Ferraro, Alessandro; Paternostro, Mauro [Queen' s University, Centre for Theoretical Atomic, Molecular, and Optical Physics, School of Mathematics and Physics, Belfast (United Kingdom); Paris, Matteo G.A. [Universita degli Studi di Milano, Dipartimento di Fisica, Milano (Italy)

    2015-12-15

    We address quantitatively the relationship between the nonlinearity of a mechanical resonator and the nonclassicality of its ground state. In particular, we analyze the nonclassical properties of the nonlinear Duffing oscillator (being driven or not) as a paradigmatic example of a nonlinear nanomechanical resonator. We first discuss how to quantify the nonlinearity of this system and then show that the nonclassicality of the ground state, as measured by the volume occupied by the negative part of the Wigner function, monotonically increases with the nonlinearity in all the working regimes addressed in our study. Our results show quantitatively that nonlinearity is a resource to create nonclassical states in mechanical systems. (orig.)

  4. Nonclassical effects in plasmonics: an energy perspective to quantify nonclassical effects

    DEFF Research Database (Denmark)

    Yan, Wei; Mortensen, N. Asger

    2016-01-01

    propose a nonclassical-impact parameter (NCI) to characterize the degree of nonclassical effects from an energy perspective, i.e., which fraction of the total electromagnetic energy is attributed to classical electrodynamic terms and which fraction is correspondingly to be assigned to nonclassical degrees...... of an infinite work function....

  5. Nonclassicality of local bipartite correlations

    Science.gov (United States)

    Jebaratnam, C.; Aravinda, S.; Srikanth, R.

    2017-03-01

    Simulating quantum nonlocality and steering requires augmenting preshared randomness with nonvanishing communication cost. This prompts the question of how one may provide such an operational characterization for the quantumness of correlations due to even unentangled states. Here we show that for a certain class of states, such quantumness can be pointed out by superlocality, the requirement for a larger dimension of the preshared randomness to simulate the correlations than that of the quantum state that generates them. This provides an approach to define the nonclassicality of local multipartite correlations in convex operational theories.

  6. Nonclassical correlations in superconducting circuits

    Energy Technology Data Exchange (ETDEWEB)

    Migliore, Rosanna [Dipartimento di Scienze Fisiche ed Astronomiche, Universita di Palermo (Italy); CNR-INFM, UdR CNISM di Palermo, Palermo (Italy); Scala, Matteo [Dipartimento di Scienze Fisiche ed Astronomiche, Universita di Palermo (Italy); Departamento de Optica, Facultad de Fisica, Universidad Complutense, Madrid (Spain); Guccione, Marina; Sanchez-Soto, Luis L. [Dipartimento di Scienze Fisiche ed Astronomiche, Universita di Palermo (Italy); Messina, Antonino [Departamento de Optica, Facultad de Fisica, Universidad Complutense, Madrid (Spain)

    2009-05-15

    A key step on the road map to solid-state quantum information processing (and to a deeper understanding of many counterintuitive aspects of quantum mechanics) is the generation and manipulation of nonclassical correlations between different quantum systems. Within this framework, we analyze the possibility of generating maximally entangled states in a system of two superconducting flux qubits, as well as the effectof their own environments on the entanglement dynamics. The analysis reported here confirms that the phenomena of sudden birth and sudden death of the entanglement do not depend on the particular measure of the entanglement adopted (copyright 2009 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  7. Transcriptional regulation by nonclassical action of thyroid hormone

    Directory of Open Access Journals (Sweden)

    Moeller Lars C

    2011-08-01

    Full Text Available Abstract Thyroid hormone (TH is essential for normal development, growth and metabolism. Its effects were thought to be principally mediated through triiodothyronine (T3, acting as a ligand for the nuclear TH receptors (TRs α and β residing on thyroid hormone response elements (TREs in the promoter of TH target genes. In this classical model of TH action, T3 binding to TRs leads to recruitment of basal transcription factors and increased transcription of TH responsive genes. Recently, the concept of TH action on gene expression has become more diverse and now includes nonclassical actions of T3 and T4: T3 has been shown to activate PI3K via the TRs, which ultimately increases transcription of certain genes, e.g. HIF-1α. Additionally, both T3 and thyroxine (T4 can bind to a membrane integrin, αvβ3, which leads to activation of the PI3K and MAPK signal transduction pathways and finally also increases gene transcription, e.g. of the FGF2 gene. Therefore, these initially nongenomic, nonclassical actions seem to serve as additional interfaces for transcriptional regulation by TH. Aim of this perspective is to summarize the genes that are currently known to be induced by nonclassical TH action and the mechanisms involved.

  8. Fisher information, nonclassicality and quantum revivals

    Science.gov (United States)

    Romera, Elvira; de los Santos, Francisco

    2013-11-01

    Wave packet revivals and fractional revivals are studied by means of a measure of nonclassicality based on the Fisher information. In particular, we show that the spreading and the regeneration of initially Gaussian wave packets in a quantum bouncer and in the infinite square-well correspond, respectively, to high and low nonclassicality values. This result is in accordance with the physical expectations that at a quantum revival wave packets almost recover their initial shape and the classical motion revives temporarily afterward.

  9. Fisher information, nonclassicality and quantum revivals

    Energy Technology Data Exchange (ETDEWEB)

    Romera, Elvira [Instituto Carlos I de Física Teórica y Computacional, Universidad de Granada, Fuentenueva s/n, 18071 Granada (Spain); Departamento de Física Atómica, Molecular y Nuclear, Universidad de Granada, Fuentenueva s/n, 18071 Granada (Spain); Santos, Francisco de los, E-mail: dlsantos@onsager.ugr.es [Instituto Carlos I de Física Teórica y Computacional, Universidad de Granada, Fuentenueva s/n, 18071 Granada (Spain); Departamento de Electromagnetismo y Física de la Materia, Universidad de Granada, Fuentenueva s/n, 18071 Granada (Spain)

    2013-11-08

    Wave packet revivals and fractional revivals are studied by means of a measure of nonclassicality based on the Fisher information. In particular, we show that the spreading and the regeneration of initially Gaussian wave packets in a quantum bouncer and in the infinite square-well correspond, respectively, to high and low nonclassicality values. This result is in accordance with the physical expectations that at a quantum revival wave packets almost recover their initial shape and the classical motion revives temporarily afterward.

  10. Teleportation of Nonclassical Wave Packets of light

    CERN Document Server

    Lee, Noriyuki; Takeno, Yuishi; Takeda, Shuntaro; Webb, James; Huntington, Elanor; Furusawa, Akira

    2012-01-01

    We report on the experimental quantum teleportation of strongly nonclassical wave packets of light. To perform this full quantum operation while preserving and retrieving the fragile non-classicality of the input state, we have developed a broadband, zero-dispersion teleportation apparatus that works in conjunction with time-resolved state preparation equipment. Our approach brings within experimental reach a whole new set of hybrid protocols involving discrete- and continuous-variable techniques in quantum information processing for optical sciences.

  11. Nonclassical gasdynamic region of selected fluorocarbons

    Science.gov (United States)

    Guardone, A.; Argrow, B. M.

    2005-11-01

    The nonclassical gasdynamic region of fluorinated substances belonging to the PP, FC, and E series is investigated using different thermodynamic models of increasing complexity. Thermodynamic models range from the simple van der Waals equation of state to the more complex Martin-Hou model and include the Redlich-Kwong, Clausius-II, Soave-Redlich-Kwong, and Peng-Robinson equations, under both the polytropic (constant isochoric specific heat in the dilute gas limit) and nonpolytropic approximations. The possibility of observing nonclassical gasdynamic behavior for a given fluid is confirmed to increase with the molecular weight of the substance times the specific heat at constant volume in the dilute gas limit and at the critical temperature, but to be almost insensitive to the nonpolytropic behavior of the fluid; the dependence on the compressibility at the critical point is also weak. A strong dependence on the acentric factor of the substance is revealed, which points to fluids made of nonpolar molecules with nearly spheroidal shapes as the most favorable to exhibit nonclassical gasdynamic behavior. In this respect, the fluorinated cyclic compounds of the PP series are singled out as the most promising candidates for the experimental verification of the existence of nonclassical phenomena in the vapor phase and for nonclassical gasdynamic applications.

  12. Entanglement and nonclassicality: A mutual impression

    Science.gov (United States)

    Gholipour, H.; Shahandeh, F.

    2016-06-01

    We find a sufficient condition to imprint the single-mode bosonic phase-space nonclassicality onto a bipartite state as modal entanglement and vice versa using an arbitrary beam splitter. Surprisingly, the entanglement produced or detected in this way depends only on the nonclassicality of the marginal input or output states, regardless of their purity and separability. In this way, our result provides a sufficient condition for generating entangled states of arbitrary high temperature and arbitrary large number of particles. We also study the evolution of the entanglement within a lossy Mach-Zehnder interferometer and show that unless both modes are totally lost, the entanglement does not diminish.

  13. Dynamics of Non-Classical Interval Exchanges

    CERN Document Server

    Gadre, Vaibhav S

    2009-01-01

    Train tracks with a single vertex are a generalization of interval exchange maps. Here, we consider non-classical interval exchanges: complete train tracks with a single vertex. These can be studied as a dynamical system by considering Rauzy induction in this context. This gives a refinement process on the parameter space similar to Kerckhoff's simplicial systems. We show that the refinement process gives an expansion that has a key dynamical property called uniform distortion. We use uniform distortion to prove normality of the expansion. Consequently we prove an analog of Keane's conjecture: almost every non-classical interval exchange is uniquely ergodic.

  14. Strictly nonclassical behavior of a mesoscopic system

    Science.gov (United States)

    Hu, Jiazhong; Vendeiro, Zachary; Chen, Wenlan; Zhang, Hao; McConnell, Robert; Sørensen, Anders S.; Vuletić, Vladan

    2017-03-01

    We experimentally demonstrate the strictly nonclassical behavior in a many-atom system using a recently derived criterion [E. Kot et al., Phys. Rev. Lett. 108, 233601 (2012), 10.1103/PhysRevLett.108.233601] that explicitly does not make use of quantum mechanics. We thereby show that the magnetic-moment distribution measured by McConnell et al. [Nature (London) 519, 439 (2015), 10.1038/nature14293] in a system with a total mass of 2.6 ×105 atomic mass units is inconsistent with classical physics. Notably, the strictly nonclassical behavior affects an area in phase space 103 times larger than the Planck quantum ℏ .

  15. Divergence en Route to Nonclassical Annonaceous Acetogenins

    DEFF Research Database (Denmark)

    Strand, Daniel; Norrby, Per-Ola; Rein, Tobias

    2006-01-01

    Syntheses of the nonclassical annonaceous acetogenins, pyranicin, and pyragonicin from common latestage intermediates are presented. The construction of key elements relies on asymmetric HWE reactions, including the desymmetrization of a meso-dialdehyde and a parallel kinetic resolution of a race...

  16. Nonclassical evolution of a free particle

    OpenAIRE

    Johansen, Lars M.

    1998-01-01

    A conditional kinetic energy is defined in terms of the Wigner distribution. It is shown that this kinetic energy may become negative for negative Wigner distributions. A free particle wave packet with negative kinetic energy will spread in a nonclassical manner.

  17. Nonclassicality in phase-number uncertainty relations

    Energy Technology Data Exchange (ETDEWEB)

    Matia-Hernando, Paloma; Luis, Alfredo [Departamento de Optica, Facultad de Ciencias Fisicas, Universidad Complutense, 28040 Madrid (Spain)

    2011-12-15

    We show that there are nonclassical states with lesser joint fluctuations of phase and number than any classical state. This is rather paradoxical since one would expect classical coherent states to be always of minimum uncertainty. The same result is obtained when we replace phase by a phase-dependent field quadrature. Number and phase uncertainties are assessed using variance and Holevo relation.

  18. Nonclassical characteristic functions for highly sensitive measurements

    CERN Document Server

    Richter, T; Richter, Th.

    2007-01-01

    Characteristic functions are shown to be useful for highly sensitive measurements. Redistributions of motional Fock states of a trapped atom can be directly monitored via the most fragile nonclassical part of the characteristic function. The method can also be used for decoherence measurements in optical quantum-information systems.

  19. On nonclassical symmetries of generalized Huxley equations

    CERN Document Server

    Ivanova, Nataliya M

    2010-01-01

    Nonclassical symmetries of a class of generalized Huxley equations of form $u_t=u_{xx}+k(x)u^2(1-u)$ are found. More precisely, for the class under consideration we completely classify reduction operators with $\\tau=1$ and give a wide number of examples of equations admitting reduction operators with $\\tau=0$.

  20. Non-classical paths in interference experiments

    CERN Document Server

    Sawant, Rahul; Sinha, Aninda; Sinha, Supurna; Sinha, Urbasi

    2014-01-01

    In a double slit interference experiment, the wave function at the screen with both slits open is not exactly equal to the sum of the wave functions with the slits individually open one at a time. The three scenarios represent three different boundary conditions and as such, the superposition principle should not be applicable. However, most well known text books in quantum mechanics implicitly and/or explicitly use this assumption which is only approximately true. In our present study, we have used the Feynman path integral formalism to quantify contributions from non-classical paths in quantum interference experiments which provide a measurable deviation from a naive application of the superposition principle. A direct experimental demonstration for the existence of these non-classical paths is hard. We find that contributions from such paths can be significant and we propose simple three-slit interference experiments to directly confirm their existence.

  1. Nonclassical Paths in Quantum Interference Experiments

    Science.gov (United States)

    Sawant, Rahul; Samuel, Joseph; Sinha, Aninda; Sinha, Supurna; Sinha, Urbasi

    2014-09-01

    In a double slit interference experiment, the wave function at the screen with both slits open is not exactly equal to the sum of the wave functions with the slits individually open one at a time. The three scenarios represent three different boundary conditions and as such, the superposition principle should not be applicable. However, most well-known text books in quantum mechanics implicitly and/or explicitly use this assumption that is only approximately true. In our present study, we have used the Feynman path integral formalism to quantify contributions from nonclassical paths in quantum interference experiments that provide a measurable deviation from a naive application of the superposition principle. A direct experimental demonstration for the existence of these nonclassical paths is difficult to present. We find that contributions from such paths can be significant and we propose simple three-slit interference experiments to directly confirm their existence.

  2. Non-Classical Inhibition of Carbonic Anhydrase

    Science.gov (United States)

    Lomelino, Carrie L.; Supuran, Claudiu T.; McKenna, Robert

    2016-01-01

    Specific isoforms from the carbonic anhydrase (CA) family of zinc metalloenzymes have been associated with a variety of diseases. Isoform-specific carbonic anhydrase inhibitors (CAIs) are therefore a major focus of attention for specific disease treatments. Classical CAIs, primarily sulfonamide-based compounds and their bioisosteres, are examined as antiglaucoma, antiepileptic, antiobesity, antineuropathic pain and anticancer compounds. However, many sulfonamide compounds inhibit all CA isoforms nonspecifically, diluting drug effectiveness and causing undesired side effects due to off-target inhibition. In addition, a small but significant percentage of the general population cannot be treated with sulfonamide-based compounds due to a sulfa allergy. Therefore, CAIs must be developed that are not only isoform specific, but also non-classical, i.e. not based on sulfonamides, sulfamates, or sulfamides. This review covers the classes of non-classical CAIs and the recent advances in the development of isoform-specific inhibitors based on phenols, polyamines, coumarins and their derivatives. PMID:27438828

  3. Nonclassical energy transfer in photosynthetic FMO complex

    Directory of Open Access Journals (Sweden)

    Abramavicius Vytautas

    2013-03-01

    Full Text Available Excitation energy transfer in a photosynthetic FMO complex has been simulated using the stochastic Schrödinger equation. Fluctuating chromophore transition energies are simulated from the quantum correlation function which allows to properly include the finite temperature. The resulting excitation dynamics shows fast thermalization of chromophore occupations into proper thermal equilibrium. The relaxation process is characterized by entropy dynamics, which shows nonclassical behavior.

  4. Treatment of Nonclassic 11-Hydroxylase Deficiency with Ashwagandha Root

    Directory of Open Access Journals (Sweden)

    Daniel Powell

    2017-01-01

    Full Text Available An elderly woman presented with acne and male pattern alopecia, which upon diagnostic evaluation was found to be due to nonclassic 11-hydroxylase deficiency. We previously reported that Ashwagandha root ameliorates nonclassic 3-β-ol dehydrogenase and aldosterone synthase deficiencies. This is the first report of its use being associated with amelioration of nonclassic 11-hydroxylase deficiency, where its apparent effects appear to be dose-related.

  5. SPRED: A machine learning approach for the identification of classical and non-classical secretory proteins in mammalian genomes

    Energy Technology Data Exchange (ETDEWEB)

    Kandaswamy, Krishna Kumar [Institute for Neuro- and Bioinformatics, University of Luebeck, 23538 Luebeck (Germany); Graduate School for Computing in Medicine and Life Sciences, University of Luebeck, 23538 Luebeck (Germany); Pugalenthi, Ganesan [School of Electrical and Electronic Engineering, Nanyang Technological University, Singapore 639798 (Singapore); Hartmann, Enno; Kalies, Kai-Uwe [Centre for Structural and Cell Biology in Medicine, Institute of Biology, University of Luebeck, 23538 Luebeck (Germany); Moeller, Steffen [Institute for Neuro- and Bioinformatics, University of Luebeck, 23538 Luebeck (Germany); Suganthan, P.N. [School of Electrical and Electronic Engineering, Nanyang Technological University, Singapore 639798 (Singapore); Martinetz, Thomas, E-mail: martinetz@inb.uni-luebeck.de [Institute for Neuro- and Bioinformatics, University of Luebeck, 23538 Luebeck (Germany)

    2010-01-15

    Eukaryotic protein secretion generally occurs via the classical secretory pathway that traverses the ER and Golgi apparatus. Secreted proteins usually contain a signal sequence with all the essential information required to target them for secretion. However, some proteins like fibroblast growth factors (FGF-1, FGF-2), interleukins (IL-1 alpha, IL-1 beta), galectins and thioredoxin are exported by an alternative pathway. This is known as leaderless or non-classical secretion and works without a signal sequence. Most computational methods for the identification of secretory proteins use the signal peptide as indicator and are therefore not able to identify substrates of non-classical secretion. In this work, we report a random forest method, SPRED, to identify secretory proteins from protein sequences irrespective of N-terminal signal peptides, thus allowing also correct classification of non-classical secretory proteins. Training was performed on a dataset containing 600 extracellular proteins and 600 cytoplasmic and/or nuclear proteins. The algorithm was tested on 180 extracellular proteins and 1380 cytoplasmic and/or nuclear proteins. We obtained 85.92% accuracy from training and 82.18% accuracy from testing. Since SPRED does not use N-terminal signals, it can detect non-classical secreted proteins by filtering those secreted proteins with an N-terminal signal by using SignalP. SPRED predicted 15 out of 19 experimentally verified non-classical secretory proteins. By scanning the entire human proteome we identified 566 protein sequences potentially undergoing non-classical secretion. The dataset and standalone version of the SPRED software is available at (http://www.inb.uni-luebeck.de/tools-demos/spred/spred).

  6. NonClassic Congenital Adrenal Hyperplasia

    Directory of Open Access Journals (Sweden)

    Azziz Ricardo

    2010-05-01

    Full Text Available Nonclassic congenital adrenal hyperplasia (NCAH due to P450c21 (21-hydroxylase deficiency is a common autosomal recessive disorder. This disorder is due to mutations in the CYP21A2 gene which is located at chromosome 6p21. The clinical features predominantly reflect androgen excess rather than adrenal insufficiency leading to an ascertainment bias favoring diagnosis in females. Treatment goals include normal linear growth velocity and "on-time" puberty in affected children. For adolescent and adult women, treatment goals include regularization of menses, prevention of progression of hirsutism, and fertility. This paper will review key aspects regarding pathophysiology, diagnosis, and treatment of NCAH.

  7. Non-classical continuum mechanics a dictionary

    CERN Document Server

    Maugin, Gérard A

    2017-01-01

    This dictionary offers clear and reliable explanations of over 100 keywords covering the entire field of non-classical continuum mechanics and generalized mechanics, including the theory of elasticity, heat conduction, thermodynamic and electromagnetic continua, as well as applied mathematics. Every entry includes the historical background and the underlying theory, basic equations and typical applications. The reference list for each entry provides a link to the original articles and the most important in-depth theoretical works. Last but not least, every entry is followed by a cross-reference to other related subject entries in the dictionary.

  8. Nonclassical Particle Transport in the 1-D Diffusive Limit

    CERN Document Server

    Vasques, Richard; Krycki, Kai

    2016-01-01

    This paper provides numerical results that demonstrate the validity of the nonclassical diffusion approximation to the nonclassical transport equation in certain 1-D diffusive systems. This result provides a more solid foundation in which to improve this theory for relevant nuclear applications.

  9. Nonclassical Symmetry Analysis of Heated Two-Dimensional Flow Problems

    Science.gov (United States)

    Naeem, Imran; Naz, Rehana; Khan, Muhammad Danish

    2015-12-01

    This article analyses the nonclassical symmetries and group invariant solution of boundary layer equations for two-dimensional heated flows. First, we derive the nonclassical symmetry determining equations with the aid of the computer package SADE. We solve these equations directly to obtain nonclassical symmetries. We follow standard procedure of computing nonclassical symmetries and consider two different scenarios, ξ1≠0 and ξ1=0, ξ2≠0. Several nonclassical symmetries are reported for both scenarios. Furthermore, numerous group invariant solutions for nonclassical symmetries are derived. The similarity variables associated with each nonclassical symmetry are computed. The similarity variables reduce the system of partial differential equations (PDEs) to a system of ordinary differential equations (ODEs) in terms of similarity variables. The reduced system of ODEs are solved to obtain group invariant solution for governing boundary layer equations for two-dimensional heated flow problems. We successfully formulate a physical problem of heat transfer analysis for fluid flow over a linearly stretching porous plat and, with suitable boundary conditions, we solve this problem.

  10. [Taxonomic theory for non-classical systematics].

    Science.gov (United States)

    Pavlinov, I Ia

    2012-01-01

    Outlined briefly are basic principles of construing general taxonomic theory for biological systematics considered in the context of non-classical scientific paradigm. The necessity of such kind of theory is substantiated, and some key points of its elaboration are exposed: its interpretation as a framework concept for the partial taxonomic theories in various schools of systematics; elaboration of idea of cognitive situation including three interrelated components, namely subject, object, and epistemic ones; its construing as a content-wisely interpreted quasi-axiomatics, with strong structuring of its conceptual space including demarcation between axioms and inferring rules; its construing as a "conceptual pyramid" of concepts of various levels of generality; inclusion of a basic model into definition of the taxonomic system (classification) regulating its content. Two problems are indicated as fundamental: definition of taxonomic diversity as a subject domain for the systematics as a whole; definition of onto-epistemological status of taxonomic system (classification) in general and of taxa in particular.

  11. Nonclassical light sources for silicon photonics

    Science.gov (United States)

    Bajoni, Daniele; Galli, Matteo

    2017-09-01

    Quantum photonics has recently attracted a lot of attention for its disruptive potential in emerging technologies like quantum cryptography, quantum communication and quantum computing. Driven by the impressive development in nanofabrication technologies and nanoscale engineering, silicon photonics has rapidly become the platform of choice for on-chip integration of high performing photonic devices, now extending their functionalities towards quantum-based applications. Focusing on quantum Information Technology (qIT) as a key application area, we review recent progress in integrated silicon-based sources of nonclassical states of light. We assess the state of the art in this growing field and highlight the challenges that need to be overcome to make quantum photonics a reliable and widespread technology.

  12. Nonclassical and semiclassical para-Bose states

    Science.gov (United States)

    Huerta Alderete, C.; Villanueva Vergara, Liliana; Rodríguez-Lara, B. M.

    2017-04-01

    Motivated by the proposal to simulate para-Bose oscillators in a trapped-ion setup [C. Huerta Alderete and B. M. Rodríguez-Lara, Phys. Rev. A 95, 013820 (2017), 10.1103/PhysRevA.95.013820], we introduce an overcomplete, nonorthogonal basis for para-Bose Hilbert spaces. The states spanning these bases can be experimentally realized in the trapped-ion simulation via time evolution. The para-Bose states show both nonclassical and semiclassical statistics on their Fock state distribution, asymmetric field quadrature variances, and do not minimize the uncertainty relation for the field quadratures. These properties are analytically controlled by the para-Bose order and the evolution time; both parameters might be feasible for fine tuning in the trapped-ion quantum simulation.

  13. Multitime correlation functions in nonclassical stochastic processes

    Science.gov (United States)

    Krumm, F.; Sperling, J.; Vogel, W.

    2016-06-01

    A general method is introduced for verifying multitime quantum correlations through the characteristic function of the time-dependent P functional that generalizes the Glauber-Sudarshan P function. Quantum correlation criteria are derived which identify quantum effects for an arbitrary number of points in time. The Magnus expansion is used to visualize the impact of the required time ordering, which becomes crucial in situations when the interaction problem is explicitly time dependent. We show that the latter affects the multi-time-characteristic function and, therefore, the temporal evolution of the nonclassicality. As an example, we apply our technique to an optical parametric process with a frequency mismatch. The resulting two-time-characteristic function yields full insight into the two-time quantum correlation properties of such a system.

  14. Sampling of quasidistributions, nonclassical behavior and negative probabilities

    Energy Technology Data Exchange (ETDEWEB)

    Peřina, J. [Department of Optics and Joint Laboratory of Optics of Palacký University and Institute of Physics of AS CR, Faculty of Science, Palacký University, 17. listopadu 12, 771 46 Olomouc (Czech Republic); Křepelka, J., E-mail: jaromir.krepelka@upol.cz [Joint Laboratory of Optics of Palacký University and Institute of Physics of AS CR, 17. listopadu 50a, 771 46 Olomouc (Czech Republic)

    2016-05-20

    Highlights: • Joint quasidistributions for parametric down conversion in nonclassical region are derived. • These quasidistributions are sampled with the use of the Shannon–Kotelnikov theorem. • The sampling is used for interpretation of negative probabilities in nonclassical region. - Abstract: We perform a sampling of the quasidistribution for the process of optical down-conversion in nonclassical regime, in which negative values of the quasidistribution are exhibited, using the Shannon–Kotelnikov sampling formula. We show that negative values of the quasidistribution do not directly represent probabilities, however, negative terms in the sampling formula related to the nonclassical behavior can be interpreted as positive probabilities in the negative orthogonal sinc-basis, whereas positive probabilities in the positive sinc-basis describe classical cases.

  15. Nonclassical Symmetries for Nonlinear Partial Differential Equations via Compatibility

    Institute of Scientific and Technical Information of China (English)

    Mostafa F. El-Sabbagh; Ahmad T. Ali

    2011-01-01

    The determining equations for the nonclassical symmetry reductions of nonlinear partial differential equations with arbitrary order can be obtained by requiring the compatibility between the original equations and the invariant surface conditions. The (2+1)-dimensional shallow water wave equation, Boussinesq equation, and the dispersive wave equations in shallow water serve as examples i11ustrating how compatibility leads quickly and easily to the determining equations for their nonclassical symmetries.

  16. Effect of relativistic motion on witnessing nonclassicality of quantum states

    Science.gov (United States)

    Checińska, Agata; Lorek, Krzysztof; Dragan, Andrzej

    2017-01-01

    We show that the operational definition of nonclassicality of a quantum state depends on the motion of the observer. We use the relativistic Unruh-DeWitt detector model to witness nonclassicality of the probed field state. It turns out that the witness based on the properties of the P representation of the quantum state depends on the trajectory of the detector. Inertial and noninertial motion of the device have qualitatively different impact on the performance of the witness.

  17. Single-mode nonclassicality criteria via Holstein-Primakoff transformation

    CERN Document Server

    Tasgin, Mehmet Emre

    2015-01-01

    Recently, two quantifications for nonclassicality of a single-mode field are shown to be equivalent; (i) the rank of entanglement it can generate by a beam-splitter and (ii) the number of terms needed to expand it as superposition of coherent states. We show that nonclassicality criteria can be obtained with an alternative approach. The rank of two-mode entanglement among 2-level identical particles converges to the rank of single-mode nonclassicality within the Holstein-Primakoff transformation, at the large particle number limit. In particular, we show that the entanglement criterion of Hillery & Zubairy converges to the Mandel's $Q$-parameter which is used to reveal nonclassicality, and spin-squeezing criterion of S{\\o}rensen et al. converges to single-mode squeezing condition. We obtain additional nonclassicality criteria not existing in the literature. We also discuss if single-mode nonclassicality can be visualized as the entanglement of space generating the photons. Moreover, in a forthcoming study...

  18. Nonclassical Congenital Adrenal Hyperplasia and Pregnancy

    Directory of Open Access Journals (Sweden)

    Neslihan Cuhaci

    2015-01-01

    Full Text Available Objective. The most common form of congenital adrenal hyperplasia (CAH is 21-hydroxylase (21-OH deficiency due to mutation of the CYP21A2 gene. Patients with nonclassical CAH (NC-CAH are usually asymptomatic at birth and typically present in late childhood, adolescence, or adulthood with symptoms of excessive androgen secretion. Subfertility is relative in NC-CAH, but the incidence of spontaneous miscarriage is higher. Here, we report a previously undiagnosed female who gave birth to a normal male child and is planning to become pregnant again. Case Report. A 32-year-old female was referred to our clinic for obesity. Her medical history revealed that she had had three pregnancies. She was planning to become pregnant again. Her laboratory results revealed that she had NC-CAH. Since her husband is the son of her aunt and she had miscarriages and intrauterin exitus in her history, their genetic analyses were performed. Conclusion. Since most patients with NC-CAH have a severe mutation, these patients may give birth to a child with the classical CAH (C-CAH if their partner is also carrying a severe mutation. Females with NC-CAH who desire pregnancy must be aware of the risk of having an infant with C-CAH.

  19. Signatures of nonclassical effects in optical tomograms

    Science.gov (United States)

    Sharmila, B.; Saumitran, K.; Lakshmibala, S.; Balakrishnan, V.

    2017-02-01

    Several nonclassical effects displayed by wave packets governed by nonlinear Hamiltonians can be identified and assessed directly from tomograms without attempting to reconstruct the Wigner function or the density matrix explicitly. We have demonstrated this for both single-mode and bipartite systems. We have shown that a wide spectrum of effects such as the revival phenomena, quadrature squeezing, and Hong-Mandel and Hillery type higher-order squeezing in a generic single-mode system and the double-well Bose-Einstein condensate (BEC) can be obtained from appropriate tomograms in a straightforward manner. We have examined the manner in which decoherence affects the nature of the state of a generic single-mode system at specific instants during temporal evolution. We have investigated entropic squeezing of the subsystem state of a bipartite system as it evolves in time, solely from tomograms. The procedures that we have demonstrated can be readily adapted to multimode systems. Further, for the double-well BEC we have identified an indicator of entanglement between subsystems that can be obtained directly from the tomogram. This mirrors the qualitative behavior of the subsystem von Neumann entropy and the subsystem linear entropy.

  20. Nonclassical nucleation and growth of inorganic nanoparticles

    Science.gov (United States)

    Lee, Jisoo; Yang, Jiwoong; Kwon, Soon Gu; Hyeon, Taeghwan

    2016-08-01

    The synthesis of nanoparticles with particular compositions and structures can lead to nanoparticles with notable physicochemical properties, thus promoting their use in various applications. In this area of nanoscience, the focus is shifting from size- and shape-uniform single-component nanoparticles to multicomponent nanoparticles with enhanced performance and/or multifunctionality. With the increasing complexity of synthetic reactions, an understanding of the formation mechanisms of the nanoparticles is needed to enable a systematic synthetic approach. This Review highlights mechanistic studies underlying the synthesis of nanoparticles, with an emphasis on nucleation and growth behaviours that are not expected from classical theories. We discuss the structural properties of nanoclusters that are of a size that bridges molecules and solids. We then describe the role of nanoclusters in the prenucleation process as well as in nonclassical nucleation models. The growth of nanoparticles via the assembly and merging of primary particles is also overviewed. Finally, we present the heterogeneous nucleation mechanisms behind the synthesis of multicomponent nanoparticles.

  1. Simplified P$_N$ Equations for Nonclassical Transport with Isotropic Scattering

    CERN Document Server

    Vasques, R

    2016-01-01

    A nonclassical diffusion approximation has been previously derived for the the one-speed nonclassical transport equation with isotropic scattering. In this paper we use an asymptotic analysis to derive more accurate diffusion approximations to the nonclassical transport equation. If the free-path distribution is given by an exponential (classical transport), these approximations reduce to the simplified P$_N$ (SP$_N$) equations; therefore, they are labeled nonclassical SP$_N$ equations.

  2. Postlesion estradiol treatment increases cortical cholinergic innervations via estrogen receptor-α dependent nonclassical estrogen signaling in vivo.

    Science.gov (United States)

    Koszegi, Zsombor; Szego, Éva M; Cheong, Rachel Y; Tolod-Kemp, Emeline; Ábrahám, István M

    2011-09-01

    17β-Estradiol (E2) treatment exerts rapid, nonclassical actions via intracellular signal transduction system in basal forebrain cholinergic (BFC) neurons in vivo. Here we examined the effect of E2 treatment on lesioned BFC neurons in ovariectomized mice and the role of E2-induced nonclassical action in this treatment. Mice given an N-methyl-d-aspartic acid (NMDA) injection into the substantia innominata-nucleus basalis magnocellularis complex (SI-NBM) exhibited cholinergic cell loss in the SI-NBM and ipsilateral cholinergic fiber loss in the cortex. A single injection of E2 after NMDA lesion did not have an effect on cholinergic cell loss in the SI-NBM, but it restored the ipsilateral cholinergic fiber density in the cortex in a time- and dose-dependent manner. The most effective cholinergic fiber restoration was observed with 33 ng/g E2 treatment at 1 h after NMDA lesion. The E2-induced cholinergic fiber restoration was absent in neuron-specific estrogen receptor-α knockout mice in vivo. Selective activation of nonclassical estrogen signaling in vivo by estren induced E2-like restorative actions. Selective blockade of the MAPK or protein kinase A pathway in vivo prevented E2's ability to restore cholinergic fiber loss. Finally, studies in intact female mice revealed an E2-induced restorative effect that was similar to that of E2-treated ovariectomized mice. These observations demonstrate that a single E2 treatment restores the BFC fiber loss in the cortex, regardless of endogenous E2 levels. They also reveal the critical role of nonclassical estrogen signaling via estrogen receptor-α and protein kinase A-MAPK pathways in E2-induced restorative action in the cholinergic system in vivo.

  3. Multiphoton catalysis with coherent state input: nonclassicality and decoherence

    Science.gov (United States)

    Hu, Li-Yun; Wu, Jia-Ni; Liao, Zeyang; Zubairy, M. Suhail

    2016-09-01

    We propose a scheme to generate a new kind of non-Gaussian state—the Laguerre polynomial excited coherent state (LPECS)—by using multiphoton catalysis with coherent state input. The nonclassical properties of the LPECS are studied in terms of nonclassical depth, Mandel’s parameter, second-order correlation, quadrature squeezing, and the negativity of the Wigner function (WF). It is found that the LPECS is highly nonclassical and its nonclassicality depends on the amplitude of the coherent state, the catalysis photon number, and the parameters of the unbalanced beam splitter (BS). In particular, the maximum degree of squeezing can be enhanced by increasing the catalysis photon number. In addition, we examine the effect of decoherence using the WF, which shows that the negative region, the characteristic time of decoherence, and the structure of the WF are affected by catalysis photon number and the parameters of the unbalanced BS. Our work provides general analysis on how to prepare polynomial quantum states, which may be useful in the fields of quantum information and quantum computation.

  4. TRAJECTORY ATTRACTORS FOR NONCLASSICAL DIFFUSION EQUATIONS WITH FADING MEMORY

    Institute of Scientific and Technical Information of China (English)

    Yonghai WANG; Lingzhi WANG

    2013-01-01

    In this article,we consider the existence of trajectory and global attractors for nonclassical diffusion equations with linear fading memory.For this purpose,we will apply the method presented by Chepyzhov and Miranville [7,8],in which the authors provide some new ideas in describing the trajectory attractors for evolution equations with memory.

  5. Negativity of the Wigner function as an indicator of nonclassicality

    CERN Document Server

    Kenfack, A; Kenfack, Anatole; Zyczkowski, Karol

    2004-01-01

    A measure of nonclassicality of quantum states based on the volume of the negative part of the Wigner function is proposed. We analyze this quantity for Fock states, squeezed displaced Fock states and cat-like states defined as coherent superposition of two Gaussian wave packets.

  6. Mistaken gender identity in non-classical congenital adrenal hyperplasia

    OpenAIRE

    Kukreti, Prerna; Kandpal, Manish; Jiloha, R C

    2014-01-01

    Gender identity is the sense of belonging that one feels for a particular sex psychologically and socially, independent of one's biological sex. There is much less systematic data on gender identity in females with congenital adrenal hyperplasia (CAH). We report a case of non-classical CAH presenting as a case of gender identity disorder.

  7. Mistaken gender identity in non-classical congenital adrenal hyperplasia.

    Science.gov (United States)

    Kukreti, Prerna; Kandpal, Manish; Jiloha, R C

    2014-04-01

    Gender identity is the sense of belonging that one feels for a particular sex psychologically and socially, independent of one's biological sex. There is much less systematic data on gender identity in females with congenital adrenal hyperplasia (CAH). We report a case of non-classical CAH presenting as a case of gender identity disorder.

  8. Role of Nonclassical Renin-angiotensin system Axis In Renal Fibrosis

    Directory of Open Access Journals (Sweden)

    Linli eLv

    2015-04-01

    Full Text Available The renin–angiotensin system (RAS is a major regulator of renal fibrosis. Besides the classical renin/Angiotensin-converting enzyme 2 (ACE2/angiotensin II (Ang II/AT1 and AT2 axis, multiple new axes have been recently described. The new members have added new dimensions to RAS, including the ACE2/ANG (1–7/Mas receptor axis, the prorenin/(prorenin receptor(PRR/intracelluar pathway axis, and the Angiotensin A (Ang A, alamandine-Mas-related G protein coupled receptor D(MrgD axis. This review summarized recent studies regarding role of the non-classical RAS axis in renal fibrosis, and its possible implications to the intervention of progression of chronic kidney disease.

  9. Genotype, phenotype and hormonal levels correlation in non-classical congenital adrenal hyperplasia.

    Science.gov (United States)

    Einaudi, S; Napolitano, E; Restivo, F; Motta, G; Baldi, M; Tuli, G; Grosso, E; Migone, N; Menegatti, E; Manieri, C

    2011-10-01

    Non-classical congenital adrenal hyperplasia (NCAH) is a morbid condition sustained by the reduced function of one of the enzymes involved in the adrenal steroid biosynthesis pathway, mainly the 21-hydroxylase. Different degrees of enzyme activity impairment determine different clinical pictures, with childhood or post-pubertal onset. The aim of this study was to evaluate the relationship between genotype, phenotype, and adrenal hormonal levels in a group of 66 patients affected by NCAH attending outpatient pediatric or endocrinological Clinics. Our findings show that age at pubarche/menarche was significantly younger, height SD score) and Δ bone age-chronological age were significantly higher in patients with a more severe enzyme activity impairment, while cutaneous androgenization and menstrual irregularities in post-pubertal girls were not related to the grading of genotype.

  10. Nonclassical Problem for Ultraparabolic Equation in Abstract Spaces

    Directory of Open Access Journals (Sweden)

    Gia Avalishvili

    2016-01-01

    Full Text Available Nonclassical problem for ultraparabolic equation with nonlocal initial condition with respect to one time variable is studied in abstract Hilbert spaces. We define the space of square integrable vector-functions with values in Hilbert spaces corresponding to the variational formulation of the nonlocal problem for ultraparabolic equation and prove trace theorem, which allows one to interpret initial conditions of the nonlocal problem. We obtain suitable a priori estimates and prove the existence and uniqueness of solution of the nonclassical problem and continuous dependence upon the data of the solution to the nonlocal problem. We consider an application of the obtained abstract results to nonlocal problem for ultraparabolic partial differential equation with second-order elliptic operator and obtain well-posedness result in Sobolev spaces.

  11. Algorithms for the nonclassical method of symmetry reductions

    CERN Document Server

    Clarkson, P A; Peter A Clarkson; Elizabeth L Mansfield

    1994-01-01

    In this article we present first an algorithm for calculating the determining equations associated with so-called "nonclassical method" of symmetry reductions (a la Bluman and Cole) for systems of partial differentail equations. This algorithm requires significantly less computation time than that standardly used, and avoids many of the difficulties commonly encountered. The proof of correctness of the algorithm is a simple application of the theory of Grobner bases. In the second part we demonstrate some algorithms which may be used to analyse, and often to solve, the resulting systems of overdetermined nonlinear PDEs. We take as our principal example a generalised Boussinesq equation, which arises in shallow water theory. Although the equation appears to be non-integrable, we obtain an exact "two-soliton" solution from a nonclassical reduction.

  12. Controversies about the Introduction of Non-Classical Logics

    Directory of Open Access Journals (Sweden)

    Angel Garrido

    2015-07-01

    Full Text Available Logic is a set of well-formed formulae, along with an inference relation. But the Classical Logic is bivalent; for this reason, very limited to solve problems with uncertainty on the data. It is well-known that Artificial Intelligence requires Logic. Because its Classical version shows too many insufficiencies, it is very necessary to introduce more sophisticated tools, as may be Non-Classical Logics; amongst them, Fuzzy Logic, Modal Logic, Non-Monotonic Logic, Para-consistent Logic, and so on. All them in the same line: against the dogmatism and the dualistic vision of the world: absolutely true vs. absolutely false, black vs. white, good or bad by nature, Yes vs. No, 0 vs.1, Full vs. Empty, etc. We attempt to analyze here some of these very interesting Classical andmodern Non-Classical Logics.

  13. Two-Mode Excited Entangled Coherent State: Nonclassicality and Entanglement

    Science.gov (United States)

    Zhang, Hao-Liang; Wu, Jia-Ni; Liu, Cun-Jin; Hu, Yin-Quan; Hu, Li-Yun

    2017-03-01

    Two-mode excited entangled coherent states (TME-ECSs) are introduced by operating repeatedly the photon-excited operator on the ECSs. It is shown that the normalization constant is related to the product of two Laguerre polynomials. The influence of the operation on nonclassical behaviour of the ECSs is investigated in terms of cross-correlation function, anti-bunching effect and the negativity of Wigner function, which show that nonclassical properties can be enhanced. In addition, inseparability properties of the TME-ECSs are discussed by using Bell inequality and concurrence. It is found that the degree of quantum entanglement of even ECSs increases with the increase of the total excited photon number, and the violation of Bell inequality can be present for both even and odd case only when the total excited photon numbers are even and odd, respectively.

  14. Advantages of nonclassical pointer states in postselected weak measurements

    CERN Document Server

    Turek, Yusuf; Shikano, Yutaka; Sun, Chang-Pu; Al-Amri, M

    2015-01-01

    We investigate, within the weak measurement theory, the advantages of non-classical pointer states over semi-classical ones for coherent, squeezed vacuum, and Schr\\"{o}inger cat states. These states are utilized as pointer state for the system operator $\\hat{A}$ with property $\\hat{A}^{2}=\\hat{I}$, where $\\hat{I}$ represents the identity operator. We calculate the ratio between the signal-to-noise ratio (SNR) of non-postselected and postselected weak measurements. The latter is used to find the quantum Fisher information for the above pointer states. The average shifts for those pointer states with arbitrary interaction strength are investigated in detail. One key result is that we find the postselected weak measurement scheme for non-classical pointer states to be superior to semi-classical ones. This can improve the precision of measurement process.

  15. Non-classical Measurement Theory: a Framework for Behavioral Sciences

    CERN Document Server

    Danilov, V I

    2006-01-01

    Instances of non-commutativity are pervasive in human behavior. In this paper, we suggest that psychological properties such as attitudes, values, preferences and beliefs may be suitably described in terms of the mathematical formalism of quantum mechanics. We expose the foundations of non-classical measurement theory building on a simple notion of orthospace and ortholattice (logic). Two axioms are formulated and the characteristic state-property duality is derived. A last axiom concerned with the impact of measurements on the state takes us with a leap toward the Hilbert space model of Quantum Mechanics. An application to behavioral sciences is proposed. First, we suggest an interpretation of the axioms and basic properties for human behavior. Then we explore an application to decision theory in an example of preference reversal. We conclude by formulating basic ingredients of a theory of actualized preferences based in non-classical measurement theory.

  16. Evolution of nonclassical MHC-dependent invariant T cells.

    Science.gov (United States)

    Edholm, Eva-Stina; Grayfer, Leon; Robert, Jacques

    2014-12-01

    TCR-mediated specific recognition of antigenic peptides in the context of classical MHC molecules is a cornerstone of adaptive immunity of jawed vertebrate. Ancillary to these interactions, the T cell repertoire also includes unconventional T cells that recognize endogenous and/or exogenous antigens in a classical MHC-unrestricted manner. Among these, the mammalian nonclassical MHC class I-restricted invariant T cell (iT) subsets, such as iNKT and MAIT cells, are now believed to be integral to immune response initiation as well as in orchestrating subsequent adaptive immunity. Until recently the evolutionary origins of these cells were unknown. Here we review our current understanding of a nonclassical MHC class I-restricted iT cell population in the amphibian Xenopus laevis. Parallels with the mammalian iNKT and MAIT cells underline the crucial biological roles of these evolutionarily ancient immune subsets.

  17. The Inverse Method Application for Non-Classical Logics

    OpenAIRE

    Pavlov, V.; Paky, V.

    2015-01-01

    Maslov’s inverse method is an automated theorem proving method: it can be used to develop computer programs that prove theorems automatically (such programs are called theorem provers). The inverse method can be applied to a wide range of logical calculi: propositional logic, first-order logic, intuitionistic logic, modal logics etc. We give a brief historical background of the inverse method, then discuss existing modifications and implementations of the inverse method for non-classical logics...

  18. Nonclassical interactions portrait in a macroscopic pedestrian flow model

    Science.gov (United States)

    Rosini, Massimiliano D.

    In this paper we describe the main characteristics of the macroscopic model for pedestrian flows introduced in [R.M. Colombo, M.D. Rosini, Pedestrian flows and non-classical shocks, Math. Methods Appl. Sci. 28 (13) (2005) 1553-1567] and recently sperimentally verified in [D. Helbing, A. Johansson, H.Z. Al-Abideen, Dynamics of crowd disasters: An empirical study, Phys. Rev. E (Statistical, Nonlinear, and Soft Matter Physics) 75 (4) (2007) 046109]. After a detailed study of all the possible wave interactions, we prove the existence of a weighted total variation that does not increase after any interaction. This is the main ingredient used in [R.M. Colombo, M.D. Rosini, Existence of nonclassical Cauchy problem modeling pedestrian flows, technical report, Brescia Department of Mathematics, 2008] to tackle the Cauchy problem through wave front tracking, see [A. Bressan, Hyperbolic Systems of Conservation Laws. The One-Dimensional Cauchy Problem, Oxford Lecture Ser. Math. Appl., vol. 20, Oxford Univ. Press, Oxford, 2000, The one-dimensional Cauchy problem; A. Bressan, The front tracking method for systems of conservation laws, in: C.M. Dafermos, E. Feireisl (Eds.), Handbook of Differential Equations; Evolutionary Equations, vol. 1, Elsevier, 2004, pp. 87-168; R.M. Colombo, Wave front tracking in systems of conservation laws, Appl. Math. 49 (6) (2004) 501-537]. From the mathematical point of view, this model is one of the few examples of conservation laws in which nonclassical solutions have a physical motivation, see [P.G. Lefloch, Hyperbolic Systems of Conservation Laws, Lectures Math. ETH Zürich, Birkhäuser, Basel, 2002, The theory of classical and nonclassical shock waves], and an existence result is available.

  19. Time-multiplexed measurements of nonclassical light at telecom wavelengths

    Science.gov (United States)

    Harder, G.; Silberhorn, C.; Rehacek, J.; Hradil, Z.; Motka, L.; Stoklasa, B.; Sánchez-Soto, L. L.

    2014-10-01

    We report the experimental reconstruction of the statistical properties of an ultrafast pulsed type II parametric down-conversion source in a periodically poled potassium titanyl phosphate waveguide at telecom wavelengths, with almost perfect photon-number correlations. We use a photon-number-resolving time-multiplexed detector based on a fiber-optical setup and a pair of avalanche photodiodes. By resorting to a germane data-pattern tomography, we assess the properties of the nonclassical light states with unprecedented precision.

  20. Nonclassical Particle Transport in 1-D Random Periodic Media

    CERN Document Server

    Vasques, Richard; Slaybaugh, Rachel N

    2016-01-01

    We investigate the accuracy of the recently proposed nonclassical transport equation. This equation contains an extra independent variable compared to the classical transport equation (the path-length $s$), and models particle transport taking place in homogenized random media in which a particle's distance-to-collision is not exponentially distributed. To solve the nonclassical equation one needs to know the $s$-dependent ensemble-averaged total cross section, $\\Sigma_t(\\mu,s)$, or its corresponding path-length distribution function, $p(\\mu,s)$. We consider a 1-D spatially periodic system consisting of alternating solid and void layers, randomly placed in the $x$-axis. We obtain an analytical expression for $p(\\mu,s)$ and use this result to compute the corresponding $\\Sigma_t(\\mu,s)$. Then, we proceed to numerically solve the nonclassical equation for different test problems in rod geometry; that is, particles can move only in the directions $\\mu=\\pm 1$. To assess the accuracy of these solutions, we produce ...

  1. Ran-dependent nuclear export mediators: a structural perspective.

    Science.gov (United States)

    Güttler, Thomas; Görlich, Dirk

    2011-08-31

    Nuclear export is an essential eukaryotic activity. It proceeds through nuclear pore complexes (NPCs) and is mediated by soluble receptors that shuttle between nucleus and cytoplasm. RanGTPase-dependent export mediators (exportins) constitute the largest class of these carriers and are functionally highly versatile. All of these exportins load their substrates in response to RanGTP binding in the nucleus and traverse NPCs as ternary RanGTP-exportin-cargo complexes to the cytoplasm, where GTP hydrolysis leads to export complex disassembly. The different exportins vary greatly in their substrate range. Recent structural studies of both protein- and RNA-specific exporters have illuminated how exportins bind their cargoes, how Ran triggers cargo loading and how export complexes are disassembled in the cytoplasm. Here, we review the current state of knowledge and highlight emerging principles as well as prevailing questions.

  2. Interplay of nonclassicality and entanglement of two-mode Gaussian fields generated in optical parametric processes

    Science.gov (United States)

    Arkhipov, Ievgen I.; Peřina, Jan; Peřina, Jan; Miranowicz, Adam

    2016-07-01

    The behavior of general nonclassical two-mode Gaussian states at a beam splitter is investigated. Single-mode nonclassicality as well as two-mode entanglement of both input and output states are analyzed suggesting their suitable quantifiers. These quantifiers are derived from local and global invariants of linear unitary two-mode transformations such that the sum of input (or output) local nonclassicality measures and entanglement measure gives a global invariant. This invariant quantifies the global nonclassicality resource. Mutual transformations of local nonclassicalities and entanglement induced by the beam splitter are analyzed considering incident noisy twin beams, single-mode noisy squeezed vacuum states, and states encompassing both squeezed states and twin beams. A rich tapestry of interesting nonclassical output states is predicted.

  3. Nonclassical light from a large number of independent single-photon emitters

    CERN Document Server

    Lachman, Lukáš; Filip, Radim

    2016-01-01

    Nonclassical quantum effects gradually reach domains of physics of large systems previously considered as purely classical. We derive a hierarchy of operational criteria suitable for a reliable detection of nonclassicality of light from an arbitrarily large ensemble of independent single-photon emitters. We show, that such large ensemble can always emit nonclassical light without any phase reference and under realistic experimental conditions including incoherent background noise. The nonclassical light from the large ensemble of the emitters can be witnessed much better than light coming from a single or a few emitters.

  4. Dynamics of Nonclassical Correlation in Interacting Qubits under Correlated Dissipative Environments

    Institute of Scientific and Technical Information of China (English)

    QIU Liang

    2011-01-01

    The dynamical evolution of nonclassical correlation in interacting qubits is investigated under the correlated dissipative environments for two classes of initial states.If the correlated decay rate equals the independent decay rate,there will be stationary nonclassical correlation between the qubits prepared initially in some separable states.When the correlated decay rate is different from the independent decay rate,the nonclassical correlation between the qubits eventually decays to zero for a certain class of initial states.Quantum entanglement is one of the most remarkable features of quantum mechanics and it plays a central role in quantum information and communication theory.There exists,however,nonclassical correlation,which is more general and more fundamental than entanglement in the sense that separable mixed states can have nonclassical correlation.Moreover,nonclassical correlation other than entanglement can be responsible for the quantum computational efficiency of deterministic quantum computation with one pure qubit.[1,2] Nonclassical correlation has also been used in other physical contexts,such as improving the efficiency of quantum Carnot engines,[3] quantum phase transition and Grover search processes.[4-6]In these contexts,nonclassical correlation could be a new resource for quantum computation.Quantum discord,the most popular measure of such correlations,was introduced by Olliver and Zurek.[7]%The dynamical evolution of nonclassical correlation in interacting qubits is investigated under the correlated dissipative environments for two classes of initial states. If the correlated decay rate equals the independent decay rate, there will be stationary nonclassical correlation between the qubits prepared initially in some separable states. When the correlated decay rate is different from the independent decay rate, the nonclassical correlation between the qubits eventually decays to zero for a certain class of initial states.

  5. Vibration of Timoshenko Beams Using Non-classical Elasticity Theories

    Directory of Open Access Journals (Sweden)

    J.V. Araújo dos Santos

    2012-01-01

    Full Text Available This paper presents a comparison among classical elasticity, nonlocal elasticity, and modified couple stress theories for free vibration analysis of Timoshenko beams. A study of the influence of rotary inertia and nonlocal parameters on fundamental and higher natural frequencies is carried out. The nonlocal natural frequencies are found to be lower than the classical ones, while the natural frequencies estimated by the modified couple stress theory are higher. The modified couple stress theory results depend on the beam cross-sectional size while those of the nonlocal theory do not. Convergence of both non-classical theories to the classical theory is observed as the beam global dimension increases.

  6. Nonclassical degrees of freedom in the Riemann Hamiltonian.

    Science.gov (United States)

    Srednicki, Mark

    2011-09-02

    The Hilbert-Pólya conjecture states that the imaginary parts of the zeros of the Riemann zeta function are eigenvalues of a quantum Hamiltonian. If so, conjectures by Katz and Sarnak put this Hamiltonian in the Altland-Zirnbauer universality class C. This implies that the system must have a nonclassical two-valued degree of freedom. In such a system, the dominant primitive periodic orbits contribute to the density of states with a phase factor of -1. This resolves a previously mysterious sign problem with the oscillatory contributions to the density of the Riemann zeros.

  7. Generating nonclassical quantum input field states with modulating filters

    Energy Technology Data Exchange (ETDEWEB)

    Gough, John E. [Aberystwyth University, Department of Physics, Aberystwyth, Wales (United Kingdom); Zhang, Guofeng [The Hong Kong Polytechnic University, Department of Applied Mathematics, Hong Kong (China)

    2015-12-15

    We give explicit constructions of quantum dynamical filters which generate nonclassical states (coherent states, cat states, shaped single and multi-photon states) of quantum optical fields as inputs to general quantum Markov systems. The filters will be quantum harmonic oscillators damped by the input fields, and we exploit the fact that the cascaded filter and system will have a Lindbladian that is naturally Wick-ordered in the filter modes. In particular the initialization of the modulating filter will determine the signal state generated. (orig.)

  8. Quantum teleportation of nonclassical wave packets: An effective multimode theory

    Energy Technology Data Exchange (ETDEWEB)

    Benichi, Hugo; Takeda, Shuntaro; Lee, Noriyuki; Furusawa, Akira [Department of Applied Physics, University of Tokyo, Tokyo (Japan)

    2011-07-15

    We develop a simple and efficient theoretical model to understand the quantum properties of broadband continuous variable quantum teleportation. We show that, if stated properly, the problem of multimode teleportation can be simplified to teleportation of a single effective mode that describes the input state temporal characteristic. Using that model, we show how the finite bandwidth of squeezing and external noise in the classical channel affect the output teleported quantum field. We choose an approach that is especially relevant for the case of non-Gaussian nonclassical quantum states and we finally back-test our model with recent experimental results.

  9. Treatment of beta amyloid 1–42 (Aβ1–42)-induced basal forebrain cholinergic damage by a non-classical estrogen signaling activator in vivo

    Science.gov (United States)

    Kwakowsky, Andrea; Potapov, Kyoko; Kim, SooHyun; Peppercorn, Katie; Tate, Warren P.; Ábrahám, István M.

    2016-01-01

    In Alzheimer’s disease (AD), there is a loss in cholinergic innervation targets of basal forebrain which has been implicated in substantial cognitive decline. Amyloid beta peptide (Aβ1–42) accumulates in AD that is highly toxic for basal forebrain cholinergic (BFC) neurons. Although the gonadal steroid estradiol is neuroprotective, the administration is associated with risk of off-target effects. Previous findings suggested that non-classical estradiol action on intracellular signaling pathways has ameliorative potential without estrogenic side effects. After Aβ1–42 injection into mouse basal forebrain, a single dose of 4-estren-3α, 17β-diol (estren), the non-classical estradiol pathway activator, restored loss of cholinergic cortical projections and also attenuated the Aβ1–42-induced learning deficits. Estren rapidly and directly phosphorylates c-AMP-response–element-binding-protein and extracellular-signal-regulated-kinase-1/2 in BFC neurons and restores the cholinergic fibers via estrogen receptor-α. These findings indicated that selective activation of non-classical intracellular estrogen signaling has a potential to treat the damage of cholinergic neurons in AD. PMID:26879842

  10. Quantum nondemolition measurement with a nonclassical meter input and an electro-optic enhancement

    DEFF Research Database (Denmark)

    Andersen, Ulrik Lund; Buchler, B.C.; Bachor, H.A.

    2002-01-01

    Optical quantum nondemolition measurements are performed using a beamsplitter with a nonclassical meter input and a electro-optic feedforward loop. The nonclassical meter input is provided by a stable 4.5 dB amplitude squeezed source generated by an optical parametric amplifier. We show...

  11. Conservation relation of nonclassicality and entanglement for Gaussian states in a beam splitter

    Science.gov (United States)

    Ge, Wenchao; Tasgin, Mehmet Emre; Zubairy, M. Suhail

    2015-11-01

    We study the relation between single-mode nonclassicality and two-mode entanglement in a beam splitter. We show that single-mode nonclassicality (the entanglement potential) of incident light cannot be transformed into two-mode entanglement completely after a single beam splitter. Some of the entanglement potential remains as single-mode nonclassicality in the two entangled output modes. Two-mode entanglement generated in the process can be equivalently quantified as an increase in the minimum uncertainty widths (or decrease in the squeezing) of the output states compared to the input states. We use the nonclassical depth and logarithmic negativity as single-mode nonclassicality and entanglement measures, respectively. We realize that a conservation relation between the two quantities can be adopted for Gaussian states, if one works in terms of uncertainty width. This conservation relation is extended to many sets of beam splitters.

  12. Superposition states for quantum nanoelectronic circuits and their nonclassical properties

    Science.gov (United States)

    Choi, Jeong Ryeol

    2016-09-01

    Quantum properties of a superposition state for a series RLC nanoelectronic circuit are investigated. Two displaced number states of the same amplitude but with opposite phases are considered as components of the superposition state. We have assumed that the capacitance of the system varies with time and a time-dependent power source is exerted on the system. The effects of displacement and a sinusoidal power source on the characteristics of the state are addressed in detail. Depending on the magnitude of the sinusoidal power source, the wave packets that propagate in charge(q)-space are more or less distorted. Provided that the displacement is sufficiently high, distinct interference structures appear in the plot of the time behavior of the probability density whenever the two components of the wave packet meet together. This is strong evidence for the advent of nonclassical properties in the system, that cannot be interpretable by the classical theory. Nonclassicality of a quantum system is not only a beneficial topic for academic interest in itself, but its results can be useful resources for quantum information and computation as well.

  13. Nonclassical mechanical states in an optomechanical micromaser analog

    Science.gov (United States)

    Nation, P. D.

    2013-11-01

    Here we show that quantum states of a mechanical oscillator can be generated in an optomechanical analog of the micromaser in the absence of any atomlike subsystem, thus exhibiting single-atom masing effects in a system composed solely of oscillator components. In the regime where the single-photon coupling strength is on the order of the cavity decay rate, a cavity mode with at most a single-excitation present gives rise to sub-Poissonian oscillator limit-cycles that generate quantum features in the steady state just above the renormalized cavity resonance frequency and mechanical sidebands. The merger of multiple stable limit-cycles markedly reduces these nonclassical signatures. Varying the cavity-resonator coupling strength, corresponding to the micromaser pump parameter, reveals transitions for the oscillator phonon number that are the hallmark of a micromaser. The connection to the micromaser allows for a physical understanding of how nonclassical states arise in this system and how best to maximize these signatures for experimental observation.

  14. Comparative exoprotein profiling of different Staphylococcus epidermidis strains reveals potential link between nonclassical protein export and virulence.

    Science.gov (United States)

    Siljamäki, Pia; Varmanen, Pekka; Kankainen, Matti; Sukura, Antti; Savijoki, Kirsi; Nyman, Tuula A

    2014-07-03

    Staphylococcus epidermidis (SE) includes commensal and pathogenic strains capable of infecting humans and animals. This study reports global exoproteome profiling of bovine mastitis strain PM221 and two human strains, commensal-type ATCC12228 and sepsis-associated RP62A. We identified 451, 395, and 518 proteins from culture supernatants of PM221, ATCC12228, and RP62A, respectively. Comparison of the identified exoproteomes revealed several strain-specific differences related to secreted antigens and adhesins, higher virulence capability for RP62A, and similarities between the PM221 and RP62A exoproteomes. The majority of the identified proteins (∼80%) were predicted to be cytoplasmic, including proteins known to be associated in membrane vesicles (MVs) in Staphylococcus aureus and immunogenic/adhesive moonlighting proteins. Enrichment of MV fractions from culture supernatants and analysis of their protein composition indicated that this nonclassical protein secretion pathway was being exploited under the conditions used and that there are strain-specific differences in nonclassical protein export. In addition, several predicted cell-surface proteins were identified in the culture media. In summary, the present study is the first in-depth exoproteome analysis of SE highlighting strain-specific factors able to contribute to virulence and adaptation.

  15. A non-classical class of variational problems

    CERN Document Server

    Cruz, Pedro A F; Zinober, Alan S I

    2009-01-01

    We study a new non-classical class of variational problems that is motivated by some recent research on the non-linear revenue problem in the field of economics. This class of problem can be set up as a maximising problem in the Calculus of Variations (CoV) or Optimal Control. However, the state value at the final fixed time, y(T), is a priori unknown and the integrand is a function of the unknown y(T). This is a non-standard CoV problem. In this paper we apply the new costate boundary conditions p(T) in the formulation of the CoV problem. We solve some sample examples in this problem class using the numerical shooting method to solve the resulting TPBVP, and incorporate the free y(T) as an additional unknown. Essentially the same results are obtained using symbolic algebra software.

  16. Non-classical radiation emission by a coherent conductor

    Science.gov (United States)

    Forgues, Jean-Charles; Gasse, Gabriel; Lupien, Christian; Reulet, Bertrand

    2016-08-01

    We report experimental evidence that the microwave electromagnetic field generated by a normal conductor, here a tunnel junction placed at ultra-low temperature, can be non-classical. By measuring the quadratures of the electromagnetic field at one or two frequencies in the GHz range, we demonstrate the existence of squeezing as well as entanglement in such radiation. In one experiment, we observe that the variance of one quadrature of the photo-assisted noise generated by the junction goes below its vacuum level. In the second experiment, we demonstrate the existence of correlations between the quadratures taken at two frequencies, which can be stronger than allowed by classical mechanics, proving that the radiation at those two frequencies are entangled. xml:lang="fr"

  17. Nonclassical congenital adrenal hyperplasia: targets of treatment and transition.

    Science.gov (United States)

    McCann-Crosby, Bonnie; Chen, Min-Jye; Lyons, Sarah K; Lin, Yuezhen; Axelrad, Marni; Dietrich, Jennifer E; Sutton, V Reid; Macias, Charles G; Gunn, Sheila; Karaviti, Lefkothea

    2014-12-01

    Nonclassical congenital adrenal hyperplasia (NCCAH) caused by 21-hydroxylase deficiency is a common autosomal recessive condition that can present with a wide range of hyperandrogenemic signs in childhood or adulthood. The management of children with NCCAH can be challenging, as no universally accepted guidelines have been established. Our goal was to evaluate the literature and develop an evidence-based guideline for the medical management of children and adolescents with NCCAH. We reviewed the published literature and used the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) system when appropriate to grade the evidence and provide recommendations for the medical management of children and adolescents with NCCAH, appropriate transition practices from pediatric to adult endocrine care, and psychological issues that should be addressed in parents and patients with NCCAH. We offer recommendations, based on the available evidence, for the management of NCCAH at the different developmental stages from diagnosis through transition to adulthood.

  18. Non-Classicality Criteria in Multi-port Interferometry

    CERN Document Server

    Rigovacca, Luca; Metcalf, Benjamin J; Walmsley, Ian A; Kim, M S

    2016-01-01

    Quantum interference lies at the basis of fundamental differences between quantum and classical behaviors. It is thus crucial to understand the boundaries between what interference patterns can be described by classical wave mechanics and what, on the other hand, can only be understood with a proper quantum mechanical description. While a lot of work has already been done for the simple case of two-mode interference, the multi-mode case has not been fully explored yet. Here we derive bounds for classical models of light fields in a general scenario of intensity interferometry, and we show how they can be violated in a quantum framework. As a consequence, this violation acts as a non-classicality witness, able to detect the presence of sources with sub-Poissonian photon-number statistics. We also derive a criterion for certifying the indivisibility of a quantum interferometer and obtain a method to simultaneously measure the average pairwise distinguishability of the input sources.

  19. Dynamics of stochastic nonclassical diffusion equations on unbounded domains

    Directory of Open Access Journals (Sweden)

    Wenqiang Zhao

    2015-11-01

    Full Text Available This article concerns the dynamics of stochastic nonclassical diffusion equation on $\\mathbb{R}^N$ perturbed by a $\\epsilon$-random term, where $\\epsilon\\in(0,1]$ is the intension of noise. By using an energy approach, we prove the asymptotic compactness of the associated random dynamical system, and then the existence of random attractors in $H^1(\\mathbb{R}^N$. Finally, we show the upper semi-continuity of random attractors at $\\epsilon=0$ in the sense of Hausdorff semi-metric in $H^1(\\mathbb{R}^N$, which implies that the obtained family of random attractors indexed by $\\epsilon$ converge to a deterministic attractor as $\\epsilon$ vanishes.

  20. Inducing nonclassical lasing via periodic drivings in circuit quantum electrodynamics.

    Science.gov (United States)

    Navarrete-Benlloch, Carlos; García-Ripoll, Juan José; Porras, Diego

    2014-11-01

    We show how a pair of superconducting qubits coupled to a microwave cavity mode can be used to engineer a single-atom laser that emits light into a nonclassical state. Our scheme relies on the dressing of the qubit-field coupling by periodic modulations of the qubit energy. In the dressed basis, the radiative decay of the first qubit becomes an effective incoherent pumping mechanism that injects energy into the system, hence turning dissipation to our advantage. A second, auxiliary qubit is used to shape the decay within the cavity, in such a way that lasing occurs in a squeezed basis of the cavity mode. We characterize the system both by mean-field theory and exact calculations. Our work may find applications in the generation of squeezing and entanglement in circuit QED, as well as in the study of dissipative few- and many-body phase transitions.

  1. q -deformed noncommutative cat states and their nonclassical properties

    Science.gov (United States)

    Dey, Sanjib

    2015-02-01

    We study several classical-like properties of q -deformed nonlinear coherent states as well as nonclassical behaviors of q -deformed version of the Schrödinger cat states in noncommutative space. Coherent states in q -deformed space are found to be minimum uncertainty states together with the squeezed photon distributions unlike the ordinary systems, where the photon distributions are always Poissonian. Several advantages of utilizing cat states in noncommutative space over the standard quantum mechanical spaces have been reported here. For instance, the q -deformed parameter has been utilized to improve the squeezing of the quadrature beyond the ordinary case. Most importantly, the parameter provides an extra degree of freedom by which we achieve both quadrature squeezed and number squeezed cat states at the same time in a single system, which is impossible to achieve from ordinary cat states.

  2. q-deformed noncommutative cat states and their nonclassical properties

    CERN Document Server

    Dey, Sanjib

    2015-01-01

    We study several classical like properties of q-deformed nonlinear coherent states as well as nonclassical behaviours of q-deformed version of the Schrodinger cat states in noncommutative space. Coherent states in q-deformed space are found to be minimum uncertainty states together with the squeezed photon distributions unlike the ordinary systems, where the photon distributions are always Poissonian. Several advantages of utilising cat states in noncommutative space over the standard quantum mechanical spaces have been reported here. For instance, the q-deformed parameter has been utilised to improve the squeezing of the quadrature beyond the ordinary case. Most importantly, the parameter provides an extra degree of freedom by which we achieve both quadrature squeezed and number squeezed cat states at the same time in a single system, which is impossible to achieve from ordinary cat states.

  3. Nonclassical properties and quantum resources of hierarchical photonic superposition states

    Energy Technology Data Exchange (ETDEWEB)

    Volkoff, T. J., E-mail: adidasty@gmail.com [University of California, Department of Chemistry (United States)

    2015-11-15

    We motivate and introduce a class of “hierarchical” quantum superposition states of N coupled quantum oscillators. Unlike other well-known multimode photonic Schrödinger-cat states such as entangled coherent states, the hierarchical superposition states are characterized as two-branch superpositions of tensor products of single-mode Schrödinger-cat states. In addition to analyzing the photon statistics and quasiprobability distributions of prominent examples of these nonclassical states, we consider their usefulness for highprecision quantum metrology of nonlinear optical Hamiltonians and quantify their mode entanglement. We propose two methods for generating hierarchical superpositions in N = 2 coupled microwave cavities, exploiting currently existing quantum optical technology for generating entanglement between spatially separated electromagnetic field modes.

  4. Materials with complex behaviour II properties, non-classical materials and new technologies

    CERN Document Server

    Oechsner, Andreas

    2012-01-01

    This book reviews developments and trends in advanced materials and their properties; modeling and simulation of non-classical materials and new technologies for joining materials. Offers tools for characterizing and predicting properties and behavior.

  5. The Rothe's Method to a Parabolic Integrodifferential Equation with a Nonclassical Boundary Conditions

    Directory of Open Access Journals (Sweden)

    Abdelfatah Bouziani

    2010-01-01

    the weak solvability of parabolic integrodifferential equations with a nonclassical boundary conditions. The investigation is made by means of approximation by the Rothes method which is based on a semidiscretization of the given problem with respect to the time variable.

  6. Protein-Phospholipid Interactions in Nonclassical Protein Secretion: Problem and Methods of Study

    Directory of Open Access Journals (Sweden)

    David Neivandt

    2013-02-01

    Full Text Available Extracellular proteins devoid of signal peptides use nonclassical secretion mechanisms for their export. These mechanisms are independent of the endoplasmic reticulum and Golgi. Some nonclassically released proteins, particularly fibroblast growth factors (FGF 1 and 2, are exported as a result of their direct translocation through the cell membrane. This process requires specific interactions of released proteins with membrane phospholipids. In this review written by a cell biologist, a structural biologist and two membrane engineers, we discuss the following subjects: (i Phenomenon of nonclassical protein release and its biological significance; (ii Composition of the FGF1 multiprotein release complex (MRC; (iii The relationship between FGF1 export and acidic phospholipid externalization; (iv Interactions of FGF1 MRC components with acidic phospholipids; (v Methods to study the transmembrane translocation of proteins; (vi Membrane models to study nonclassical protein release.

  7. Nonclassical Photon Pairs Generated from a Room-temperature Atomic Ensemble

    Institute of Scientific and Technical Information of China (English)

    JIANG Wei; HAN Chao; XUE Peng; DUAN L M; GUO G C

    2004-01-01

    @@ We report experimental generation of non-classically correlated photon pairs from collective emission in a room temperature atomic vapor cell.The nonclassical feature of the emission is demonstrated by observing a violation of the Cauchy-Schwarz inequality.Each pair of correlated photons are separated by a controllable time delay up to 2 microseconds.This experiment demonstrates an important step towards the realization of the Duan-Lukin-Cirac-Zoller scheme for scalable long-distance quantum communication.

  8. Generation of Hidden Optical-Polarization: Squeezing and Non-Classicality

    OpenAIRE

    Gupta, Gyaneshwar K.; Kumar, Akhilesh; Singh, Ravi S

    2010-01-01

    A monochromatic double-mode coherent light endowed with orthogonally polarized photons propagating collinearly is studied in Degenerate Parametric Amplification. Generation of Hidden Optical- Polarized States is shown by non-zero values of Index of Hidden Optical-Polarization. Squeezing in HOPS is demonstrated by recognizing a Squeezing function. The Non-Classical feature of HOPS is observed by 'degree of Hidden Optical-Polarization' which attains non-classical value 'greater than unity'. The...

  9. Quantitative characterization of non-classic polarization of cations on clay aggregate stability.

    Directory of Open Access Journals (Sweden)

    Feinan Hu

    Full Text Available Soil particle interactions are strongly influenced by the concentration, valence and ion species and the pH of the bulk solution, which will also affect aggregate stability and particle transport. In this study, we investigated clay aggregate stability in the presence of different alkali ions (Li+, Na+, K+, and Cs+ at concentrations from10-5 to 10-1 mol L-1. Strong specific ion effects on clay aggregate stability were observed, and showed the order Cs+>K+>Na+>Li+. We found that it was not the effects of ion size, hydration, and dispersion forces in the cation-surface interactions but strong non-classic polarization of adsorbed cations that resulted in these specific effects. In this study, the non-classic dipole moments of each cation species resulting from the non-classic polarization were estimated. By comparing non-classic dipole moments with classic values, the observed dipole moments of adsorbed cations were up to 104 times larger than the classic values for the same cation. The observed non-classic dipole moments sharply increased with decreasing electrolyte concentration. We conclude that strong non-classic polarization could significantly suppress the thickness of the diffuse layer, thereby weakening the electric field near the clay surface and resulting in improved clay aggregate stability. Even though we only demonstrated specific ion effects on aggregate stability with several alkali ions, our results indicate that these effects could be universally important in soil aggregate stability.

  10. Non-classical state engineering for quantum networks

    Energy Technology Data Exchange (ETDEWEB)

    Vollmer, Christina E.

    2014-01-24

    The wide field of quantum information processing and quantum networks has developed very fast in the last two decades. Besides the regime of discrete variables, which was developed first, the regime of continuous variables represents an alternative approach to realize many quantum applications. Non-classical states of light, like squeezed or entangled states, are a fundamental resource for quantum applications like quantum repeaters, quantum memories, quantum key distribution, quantum spectroscopy, and quantum metrology. These states can be generated successfully in the infrared wavelength regime. However, for some tasks other wavelengths, especially in the visible wavelength regime, are desirable. To generate non-classical states of light in this wavelength regime frequency up-conversion can be used, since all quantum properties are maintained in this process. The first part of this thesis deals with the experimental frequency up-conversion of quantum states. Squeezed vacuum states of light at 1550 nm were up-converted to 532 nm and a noise reduction of -1.5 dB at 532 nm was achieved. These states can be used for increasing the sensitivity of gravitational wave detectors or spectroscopic measurements. Furthermore, one part of an entangled state at 1550 nm was up-converted to 532 nm and, thus, entanglement between these two wavelengths was generated and characterized to -1.4 dB following Duan et al. With such a quantum link it is possible to establish a quantum network, which takes advantage of the low optical loss at 1550 nm for information transmission and of atomic transitions around 532 nm for a quantum memory in a quantum repeater. For quantum networks the distribution of entanglement and especially of a quantum key is essential. In the second part of this thesis the experimental distribution of entanglement by separable states is demonstrated. The underlying protocol requires a special three-mode state, which is separable in two of the three splittings. With

  11. Nonlinear Quantum Optical Springs and Their Nonclassical Properties

    Institute of Scientific and Technical Information of China (English)

    M.J. Faghihi; M.K. Tavassoly

    2011-01-01

    The original idea of quantum optical spring arises from the requirement of quantization of the frequency of oscillations in the Hamiltonian of harmonic oscillator. This purpose is achieved by considering a spring whose constant (and so its frequency) depends on the quantum states ofanother system. Recently, it is realized that by the assumption of frequency modulation of ω to ω √1+ μα+α the mentioned idea can be established. In the present paper, we generalize the approach of quantum optical spring with particular attention to the dependence or trequency to the intensity of radiation field that naturally observes in the nonlinear coherent states, from which we arrive at a physical system has been called by us as nonlinear quantum optical spring. Then, after the introduction of the generalized tlamiltonian of nonlinear quantum optical spring and it's solution, we will investigate the nonclassical properties of the obtained states. Specially, typical collapse and revival in the distribution functions and squeezing parameters, as particular quantum features, will be revealed.

  12. Multi-crack imaging using nonclassical nonlinear acoustic method

    Science.gov (United States)

    Zhang, Lue; Zhang, Ying; Liu, Xiao-Zhou; Gong, Xiu-Fen

    2014-10-01

    Solid materials with cracks exhibit the nonclassical nonlinear acoustical behavior. The micro-defects in solid materials can be detected by nonlinear elastic wave spectroscopy (NEWS) method with a time-reversal (TR) mirror. While defects lie in viscoelastic solid material with different distances from one another, the nonlinear and hysteretic stress—strain relation is established with Preisach—Mayergoyz (PM) model in crack zone. Pulse inversion (PI) and TR methods are used in numerical simulation and defect locations can be determined from images obtained by the maximum value. Since false-positive defects might appear and degrade the imaging when the defects are located quite closely, the maximum value imaging with a time window is introduced to analyze how defects affect each other and how the fake one occurs. Furthermore, NEWS-TR-NEWS method is put forward to improve NEWS-TR scheme, with another forward propagation (NEWS) added to the existing phases (NEWS and TR). In the added phase, scanner locations are determined by locations of all defects imaged in previous phases, so that whether an imaged defect is real can be deduced. NEWS-TR-NEWS method is proved to be effective to distinguish real defects from the false-positive ones. Moreover, it is also helpful to detect the crack that is weaker than others during imaging procedure.

  13. Rodent Models of Non-classical Progesterone Action Regulating Ovulation

    Directory of Open Access Journals (Sweden)

    Melinda A. Mittelman-Smith

    2017-07-01

    Full Text Available It is becoming clear that steroid hormones act not only by binding to nuclear receptors that associate with specific response elements in the nucleus but also by binding to receptors on the cell membrane. In this newly discovered manner, steroid hormones can initiate intracellular signaling cascades which elicit rapid effects such as release of internal calcium stores and activation of kinases. We have learned much about the translocation and signaling of steroid hormone receptors from investigations into estrogen receptor α, which can be trafficked to, and signal from, the cell membrane. It is now clear that progesterone (P4 can also elicit effects that cannot be exclusively explained by transcriptional changes. Similar to E2 and its receptors, P4 can initiate signaling at the cell membrane, both through progesterone receptor and via a host of newly discovered membrane receptors (e.g., membrane progesterone receptors, progesterone receptor membrane components. This review discusses the parallels between neurotransmitter-like E2 action and the more recently investigated non-classical P4 signaling, in the context of reproductive behaviors in the rodent.

  14. Nonclassic congenital adrenal hyperplasia misdiagnosed as Turner syndrome.

    Science.gov (United States)

    Mishra, Vineet V; Pritti, Kumari; Aggarwal, Rohina; Choudhary, Sumesh

    2015-01-01

    We present a patient with nonclassic congenital adrenal hyperplasia (NCAH) misdiagnosed as mosaic Turner syndrome. She presented with complaints of primary infertility. Short stature, the presence of facial hair and hoarse voice was also noted. She had primary amenorrhea and was advised for karyotype at 16 years of age, which was reported as 45, X[20]/46, XX[80], stating her as a case of mosaic Turner syndrome. Clitoroplasty was done at 21 years of age for clitoromegaly, which was noticed during puberty. The diagnosis of mosaic Turner could not explain the virilization. Therefore, we repeated the karyotype, which revealed 46, XX in more than 100 metaphases and was sufficient to exclude mosaicism. Furthermore, the endocrinological evaluation revealed high testosterone level with a normal 17 alpha-hydroxyprogesterone (17-OHP). The presence of pubertal onset virilization with a karyotype of 46, XX and raised testosterone level with normal 17-OHP level, raised the suspicion of NCAH for which adrenocorticotropic hormone stimulation test was done which confirmed the diagnosis of NCAH.

  15. Non-classical export of an adenovirus structural protein.

    Science.gov (United States)

    Trotman, Lloyd C; Achermann, Dominik P; Keller, Stephan; Straub, Monika; Greber, Urs F

    2003-06-01

    The icosahedral capsids of Adenoviruses (Ads) consist of the hexon and stabilizing proteins building the facettes, and of the vertex protein penton base (Pb) anchoring the protruding fibers. The fibers bind to the Coxsackie virus B Ad cell surface receptor (CAR) and Pb to integrins. Here we describe a novel property of the Ad2 Pb. Pb was found to leave the infected cell and, upon exit, it attached to the surrounding noninfected cells forming a radial gradient with highest Pb levels on cells adjacent to the infected cell. The producer cells remained intact until at least 30 h post infection. At this point, Pb was not recovered from the extracellular medium, suggesting that its cell-cell spread might not involve free Pb. When viral particles were released at late stages of infection, soluble Pb was found in the extracellular medium and it randomly bound to noninfected cells. Nonlytic export of Pb occurred upon transient transfection with plasmid DNA, but plasmid-encoded fiber was not exported, indicating that cell-cell spread of Pb is autonomous of infection. Pb export was not affected by Brefeldin A-induced disruption of the Golgi apparatus, suggesting that it occurred via a nonclassical mechanism. Interestingly, the coexpression of Pb and fiber leads to both Pb and fiber export, termed 'protein abduction'. We suggest that fiber abduction might support viral dissemination in infected tissues by interfering with tissue integrity.

  16. Nonclassic congenital adrenal hyperplasia misdiagnosed as Turner syndrome

    Directory of Open Access Journals (Sweden)

    Vineet V Mishra

    2015-01-01

    Full Text Available We present a patient with nonclassic congenital adrenal hyperplasia (NCAH misdiagnosed as mosaic Turner syndrome. She presented with complaints of primary infertility. Short stature, the presence of facial hair and hoarse voice was also noted. She had primary amenorrhea and was advised for karyotype at 16 years of age, which was reported as 45, X[20]/46, XX[80], stating her as a case of mosaic Turner syndrome. Clitoroplasty was done at 21 years of age for clitoromegaly, which was noticed during puberty. The diagnosis of mosaic Turner could not explain the virilization. Therefore, we repeated the karyotype, which revealed 46, XX in more than 100 metaphases and was sufficient to exclude mosaicism. Furthermore, the endocrinological evaluation revealed high testosterone level with a normal 17 alpha-hydroxyprogesterone (17-OHP. The presence of pubertal onset virilization with a karyotype of 46, XX and raised testosterone level with normal 17-OHP level, raised the suspicion of NCAH for which adrenocorticotropic hormone stimulation test was done which confirmed the diagnosis of NCAH.

  17. Non-classical method of modelling of vibrating mechatronic systems

    Science.gov (United States)

    Białas, K.; Buchacz, A.

    2016-08-01

    This work presents non-classical method of modelling of mechatronic systems by using polar graphs. The use of such a method enables the analysis and synthesis of mechatronic systems irrespective of the type and number of the elements of such a system. The method id connected with algebra of structural numbers. The purpose of this paper is also introduces synthesis of mechatronic system which is the reverse task of dynamics. The result of synthesis is obtaining system meeting the defined requirements. This approach is understood as design of mechatronic systems. The synthesis may also be applied to modify the already existing systems in order to achieve a desired result. The system was consisted from mechanical and electrical elements. Electrical elements were used as subsystem reducing unwanted vibration of mechanical system. The majority of vibration occurring in devices and machines is harmful and has a disadvantageous effect on their condition. Harmful impact of vibration is caused by the occurrence of increased stresses and the loss of energy, which results in faster wear machinery. Vibration, particularly low-frequency vibration, also has a negative influence on the human organism. For this reason many scientists in various research centres conduct research aimed at the reduction or total elimination of vibration.

  18. A non-classical view of the modulation of mineral precipitation by organic additives

    Science.gov (United States)

    Ruiz-Agudo, Encarnacion; Ruiz-Agudo, Cristina; Burgos-Cara, Alejandro; Putnis, Christine; Rodriguez-Navarro, Carlos; Putnis, Andrew

    2016-04-01

    Questions persist on the mechanisms of crystallization of sparingly soluble minerals such as calcium carbonate, calcium oxalate or barium sulphate. Compared to CaCO3, the mechanisms of nucleation and growth in the CaC2O4-H2O or BaSO4-H2O systems have received less attention. These phases are important due to their relevance as biominerals and/or unwanted mineral deposits in technological applications. Growing evidence suggests that sparingly soluble salts form by non-classical nucleation and growth pathways, where pre-nucleation ion associates and amorphous (solid or liquid) precursor phase(s) play a critical role (e.g. Rodríguez-Navarro et al. (2015), Ruiz-Agudo et al. (2015)). Indeed the identification of pre-nucleation species in these systems and their strong interactions with organic compounds (Verch et al. 2011) raises the possibility that the control of organics on biomineralization may begin even earlier than previously thought. A sound knowledge of the physical mechanisms by which acidic macromolecules affect nucleation and early growth may offer general insights concerning the molecular control of biomineralization, as well as being critical for improving strategies to control unwanted mineral deposition or for the synthesis of biomimetic materials. Here we present investigations on the initial stages of the precipitation of these relevant minerals in organic-free solutions to identify the precipitation pathway and to look for any potential precursor phase(s) to the final, crystalline polymorph. As well, we explore the effects that several acidic organic compounds have on the different precipitation stages identified. We find that organic additives such as citric acid, polyacrilic acid or a commercial copolymer of maleic acid/allyl sulfonic acid with phosphonate groups can be active at modifying pre-nucleation stages (destabilizing of pre-nucleation species or hampering the aggregation and growth of pre-nucleation associates) and subsequently strongly

  19. On the observation of nonclassical excitations in Bose-Einstein condensates

    CERN Document Server

    Finke, Andreas; Weinfurtner, Silke

    2016-01-01

    In the recent experimental and theoretical literature well-established nonclassicality criteria from the field of quantum optics have been directly applied to the case of excitations in matter-waves. Among these are violations of Cauchy-Schwarz inequalities, Glauber-Sudarshan P-nonclassicality, sub-Poissonian number-difference squeezing (also known as the two-mode variance) and the criterion of nonseparability. We review the strong connection of these criteria and their meaning in quantum optics, and point out differences in the interpretation between light and matter waves. We then calculate observables for a homogenous Bose-Einstein condensate undergoing an arbitrary modulation in the interaction parameter at finite initial temperature, within both the quantum theory as well as a classical reference. We conclude that to date in experiments relevant for analogue gravity, nonclassical effects have not conclusively been observed and conjecture that additional, noncommuting, observables have to be measured to t...

  20. Nonclassical and Postnonclassical epistemology in Lev Vygotsky’s cultural-historical approach to clinical psychology

    Directory of Open Access Journals (Sweden)

    Zinchenko Y.P.

    2013-01-01

    Full Text Available The work presents historiographic and theoretical methodological study of establishment of fundamental theses of L.S. Vygotsky’s cultural-historical concept within the field of clinical psychology.We prove potency in application of contemporary philosophical concepts, which help distinguish between the types of scientific rationality (classical, nonclassical, and postnonclassical, for scientific reflection over the development of psychology and designation of paradigmatic status of cultural-historic concept suggested by L.S. Vygotsky and Vygotsky-Luria syndrome approach at the contemporary stage of science.Present study of scientific works of L.S. Vygotsky and his followers demonstrated that fundamentals of cultural-historic conception suggested by L.S. Vygotsky and further developed in methodology of Vygotsky-Luria syndrome approach, these fundamentals presented the origins of not only non-classical, but as well post-nonclassical model of scientific rationality. They are characterized by post-nonclassical understanding of the object and method of psychological study and post-nonclassical mode of thinking of the scientists.As it was showed, in works of L.S. Vygotsky there formulated general methodological requirements to organization of mental studies, which, on the whole, go in tune with the requirements introduced for study of complex self-developing systems. There were produced arguments to prove that the concept of Vygotsky-Luria syndrome approach describes mental syndromes as dynamic structures, which display the features of self-organization, self-determination and adaptive rationality. Hence, they can be regarded as open self-developing systems.We assume and verify the hypothesis that the syndrome analysis, due to the features of post-nonclassic modeling of scientific rationality it reveals, may be regarded as theoretically productive methodological approach at the modern stage of science.

  1. Common Vocal Effects and Partial Glottal Vibration in Professional Nonclassical Singers.

    Science.gov (United States)

    Caffier, Philipp P; Ibrahim Nasr, Ahmed; Ropero Rendon, Maria Del Mar; Wienhausen, Sascha; Forbes, Eleanor; Seidner, Wolfram; Nawka, Tadeus

    2017-07-12

    To multidimensionally investigate common vocal effects in experienced professional nonclassical singers, to examine their mechanism of production and reproducibility, to demonstrate the existence of partial glottal vibration, and to assess the potential of damage to the voice from nonclassical singing. Individual cohort study. Ten male singers aged between 25 and 46 years (34 ± 7 years [mean ± SD]) with different stylistic backgrounds were recruited (five pop/rock/metal, five musical theater). Participants repeatedly presented the usual nonclassical vocal effects and techniques in their repertoire. All performances were documented and analyzed using established instruments (eg, auditory-perceptual assessment, videolaryngostroboscopy, electroglottography, voice function diagnostics). The vocal apparatus of all singers was healthy and capable of high performance. Typical nonclassical vocal effects were breathy voice, creaky voice, vocal fry, grunting, distortion, rattle, belt, and twang. All effects could be easily differentiated from each other. They were intraindividually consistently repeatable and also interindividually produced in a similar manner. A special feature in one singer was the first evidence of partial glottal vibration when belting in the high register. The unintended transition to this reduced voice quality was accompanied by physical fatigue and inflexible respiratory support. The long-lasting use of the investigated nonclassical vocal effects had no negative impact on trained singers. The possibility of long-term damage depends on the individual constitution, specific use, duration, and extent of the hyperfunction. The incidence of partial glottal vibration and its consequences require continuing research to learn more about efficient and healthy vocal function in nonclassical singing. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  2. Infrared spectroscopy of nonclassical ions and their complexes

    Energy Technology Data Exchange (ETDEWEB)

    Boo, Doo Wan [Univ. of California, Berkeley, CA (United States)

    1995-01-01

    This thesis describes an infrared spectroscopic study on the structures and dynamics of the nonclassical ions and their complexes, using ion trap vibrational predissociation spectroscopy. Chapter One provides an introduction to the experimental apparatus used in this work. Chapter Two describes the previous theoretical and experimental works on the carbonium ion CH5+ and infrared spectroscopic and theoretical works on CH5+. CH5+ was predicted to scramble constantly without possessing a stable structure. In Chapter Three, the infrared spectroscopy for the molecular hydrogen solvated carbonium ions CH5+(H2)n (n=1-6) in the frequency region of 2700-4200 cm-1 are presented and compared with the results of ab initio molecular dynamics simulation on CH5+(H2)n (n=0-3). The results suggested that the scrambling of CH5+ slowed down considerably by the stabilization effects of the solvent H2 molecules, and it was completely frozen out when the first three H2 molecules were bound to the core CH5+. Chapter Four presents the complete infrared spectra for the solvated carbonium ions, CH5+(A)x(B)y (A,B=H2, Ar, N2, CH4;x,y=0-5) in the frequency region of 2500-3200 cm-1. As the binding affinities of the solvent molecules and the number of the solvent molecules in the clusters increased, the scrambling of CH5+ slowed down substantially. The structures of the solvated carbonium ions and the evidence for rapid proton transfer in CH5+(CH4) were also presented. Chapter Five presents the vib-rotational spectrum for the H-H stretching mode of the silanium ion SiH5+. The results suggested that Si

  3. On precise time integration method for non-classically damped MDOF systems

    Institute of Scientific and Technical Information of China (English)

    Wang Mengfu; Zhou Xiyuan

    2006-01-01

    In the complex mode superposition method, the equations of motion for non-classically damped multipledegree-of-freedom (MDOF) discrete systems can be transferred into a combination of some generalized SDOF complex oscillators. Based on the state space theory, a precise recurrence relationship for these complex oscillators is set up; then a delicate general solution of non-classically damped MDOF systems, completely in real value form, is presented in this paper.In the proposed method, no calculation of the matrix exponential function is needed and the algorithm is unconditionally stable. A numerical example is given to demonstrate the validity and efficiency of the proposed method.

  4. "Nonclassical" secretion of annexin A2 to the lumenal side of the enterocyte brush border membrane

    DEFF Research Database (Denmark)

    Danielsen, E Michael; van Deurs, Bo; Hansen, Gert H

    2003-01-01

    side of the microvilli, showing an apical secretion by a "nonclassical" mechanism. In addition, annexin A2 was associated with surface-connected, deep apical tubules in the apical terminal web region and with an underlying pleiomorphic, tubulo-vesicular compartment (subapical compartment...

  5. Food Stamps and Food Insecurity: What Can Be Learned in the Presence of Nonclassical Measurement Error?

    Science.gov (United States)

    Gundersen, Craig; Kreider, Brent

    2008-01-01

    Policymakers have been puzzled to observe that food stamp households appear more likely to be food insecure than observationally similar eligible nonparticipating households. We reexamine this issue allowing for nonclassical reporting errors in food stamp participation and food insecurity. Extending the literature on partially identified…

  6. Influences on the Talent Development Process of Non-Classical Musicians: Psychological, Social and Environmental Influences

    Science.gov (United States)

    Kamin, Sara; Richards, Hugh; Collins, Dave

    2007-01-01

    Twelve professional, non-classical musicians were interviewed about the impact of internal and external factors on their development as musicians. The data were qualitatively analyzed, and observations concerning psychological characteristics of developing excellence (PCDEs), social and environmental influences are reported. The insights of the…

  7. Disjoint nonclassical hydrocarbons have very unstable lowest-lying singlet states: a PM3 study

    Directory of Open Access Journals (Sweden)

    Richard Francis Langler

    2001-12-01

    Full Text Available Earlier workers have suggested that disjoint hydrocarbons have nearly-degenerate lowest-lying singlet and triplet states while non-disjoint (or joint hydrocarbons should be ground-state triplets. PM3 results for an appropriate selection of alternant hydrocarbons are inconsistent with that generalization: disjoint, nonclassical, alternant hydrocarbons show the strongest predilection for triplet ground states.

  8. Generation of non-classical optical fields by a beam splitter with second-order nonlinearity

    CERN Document Server

    Prakash, Hari

    2016-01-01

    We propose quantum-mechanical model of a beam splitter with second-order nonlinearity and show that non-classical features such as squeezing and sub-Poissonian photon statistics of optical fields can be generated in output fundamental and second harmonic modes when we mix coherent light beams via such a nonlinear beam splitter.

  9. Molecular interpretation of nonclassical gas dynamics of dense vapors under the van der Waals model

    NARCIS (Netherlands)

    Colonna, P.; Guardone, A.

    2006-01-01

    The van der Waals polytropic gas model is used to investigate the role of attractive and repulsive intermolecular forces and the influence of molecular complexity on the possible nonclassical gas dynamic behavior of vapors near the liquid-vapor saturation curve. The decrease of the sound speed upon

  10. A NONCLASSICAL LAW OF ITERATED LOGARITHM FOR NEGATIVELY ASSOCIATED RANDOM VARIABLES

    Institute of Scientific and Technical Information of China (English)

    JiangYe

    2003-01-01

    A nonclassical law of iterated logarithm that holds for a stationary negatively associated sequence of random variables with finite variance is proved in this paper.The proof is based on a Rosenthal type maximal inequality and the subsequence method.This result extends the work of Klesov,Rosalsky(2001)and Shao.Su(1999).

  11. Investigating the non-classical boundary conditions relevant to strain gradient theories

    Science.gov (United States)

    Jafari, Akbar; Ezzati, Meysam

    2017-02-01

    In the present study, two classes of non-classical constitutive equations consisting of the first and the second order strain gradients theories (FSG and SSG) were applied in order to develop the governing equations of static and free vibrational behavior of beam structures. The governing equations in orders of six and eight were constructed for FSG and SSG theories, respectively. Therefore, higher order or in other words non-classical boundary conditions (HOBCs or NCBCs) came into play in addition to the classical ones (CBCs). Some explanations were presented about the concept of the non-classical boundary conditions. Analytical and finite element (FE) approaches were employed to solve the governing equations. The analytical solutions were utilized in validation and convergence study of FE results. Comparisons were made with the relevant data reported in the open literature; however, to the best of the authors' knowledge, few references have been published on SSG theory and HOBCs. In the numerical studies, the effects of applying different combinations of CBCs and HOBCs to the static and free vibration behaviors of the beam were investigated. Moreover, the impacts of non-classical elastic constants and the beam size on its behavior were also studied.

  12. Beating the Abbe diffraction limit in confocal microscopy via nonclassical photon statistics.

    Science.gov (United States)

    Gatto Monticone, D; Katamadze, K; Traina, P; Moreva, E; Forneris, J; Ruo-Berchera, I; Olivero, P; Degiovanni, I P; Brida, G; Genovese, M

    2014-10-03

    We experimentally demonstrate quantum enhanced resolution in confocal fluorescence microscopy exploiting the nonclassical photon statistics of single nitrogen-vacancy color centers in diamond. By developing a general model of superresolution based on the direct sampling of the kth-order autocorrelation function of the photoluminescence signal, we show the possibility to resolve, in principle, arbitrarily close emitting centers.

  13. Negativity of the Wigner function as an indicator of non-classicality

    Energy Technology Data Exchange (ETDEWEB)

    Kenfack, Anatole [Max Planck Institute for the Physics of Complex Systems, Noethnitzerstrasse 38, 01187 Dresden (Germany); Zyczkowski, Karol [Instytut Fizyki imienia Mariana Smoluchowskiego, Uniwersytet Jagiellonski, ulica Reymonta 4, 30-059 Cracow (Poland)

    2004-10-01

    A measure of non-classicality of quantum states based on the volume of the negative part of the Wigner function is proposed. We analyse this quantity for Fock states, squeezed displaced Fock states and cat-like states defined as coherent superposition of two Gaussian wavepackets.

  14. Molecular interpretation of nonclassical gas dynamics of dense vapors under the van der Waals model

    NARCIS (Netherlands)

    Colonna, P.; Guardone, A.

    2006-01-01

    The van der Waals polytropic gas model is used to investigate the role of attractive and repulsive intermolecular forces and the influence of molecular complexity on the possible nonclassical gas dynamic behavior of vapors near the liquid-vapor saturation curve. The decrease of the sound speed upon

  15. Nanoparticle-mediated nonclassical crystal growth of sodium fluorosilicate nanowires and nanoplates

    Directory of Open Access Journals (Sweden)

    Hongxia Li

    2011-12-01

    Full Text Available We observed nonclassical crystal growth of the sodium fluorosilicate nanowires, nanoplates, and hierarchical structures through self-assembly and aggregation of primary intermediate nanoparticles. Unlike traditional ion-by-ion crystallization, the primary nanoparticles formed first and their subsequent self-assembly, fusion, and crystallization generated various final crystals. These findings offer direct evidences for the aggregation-based crystallization mechanism.

  16. Nonclassical Effects of a Four-Level Excited-Doublet Atom Model

    Institute of Scientific and Technical Information of China (English)

    ZHANG Jian-Song; XU Jing-Bo

    2006-01-01

    We adopt a dynamical algebraic method to study a four-level excited-doublet atom model and obtain the explicit expressions of the time-evolution operator and the density operator for the system. The nonclassical effects of the system, such as collapses and revivals of the atomic inversion and squeezing of the radiation field, are also discussed.

  17. Absence of clinically relevant growth acceleration in untreated children with non-classical congenital adrenal hyperplasia.

    NARCIS (Netherlands)

    Pijnenburg-Kleizen, K.J.; Borm, G.F.; Otten, B.J.; Schott, D.A.; Akker, E.L. van den; Stokvis-Brantsma, W.H.; Voorhoeve, P.G.; Bakker, B.; Claahsen-van der Grinten, H.L.

    2012-01-01

    BACKGROUND/AIMS: In classical congenital adrenal hyperplasia (CAH), elevation of adrenal androgens leads to accelerated growth and bone maturation with compromised adult height. In untreated children with non-classical CAH (NC-CAH), in which adrenal androgens are generally only slightly increased, g

  18. REGULATION OF NONCLASSICAL FGF1 RELEASE AND FGF-DEPENDENT CELL TRANSFORMATION BY CBF1-MEDIATED NOTCH SIGNALING

    Science.gov (United States)

    Kacer, Doreen; McIntire, Christian; Kirov, Alek; Kany, Erin; Roth, Jennifer; Liaw, Lucy; Small, Deena; Friesel, Robert; Basilico, Claudio; Tarantini, Francesca; Verdi, Joseph; Prudovsky, Igor

    2011-01-01

    FGF1, a widely expressed proangiogenic factor involved in tissue repair and carcinogenesis, is released from cells through a nonclassical pathway independent of endoplasmic reticulum and Golgi. Although several proteins participating in FGF1 export were identified, genetic mechanisms regulating this process remained obscure. We found that FGF1 export and expression are regulated through Notch signaling mediated by transcription factor CBF1and its partner MAML. The expression of a dominant negative (dn) form of CBF1 in 3T3 cells induces transcription of FGF1 and sphingosine kinase 1 (SphK1), which is a component of FGF1 export pathway. dnCBF1 expression stimulates the stress-independent release of transduced FGF1 from NIH 3T3 cells and endogenous FGF1 from A375 melanoma cells. NIH 3T3 cells transfected with dnCBF1 form colonies in soft agar and produce rapidly growing highly angiogenic tumors in nude mice. The transformed phenotype of dnCBF1 transfected cells is efficiently blocked by dn forms of FGF receptor 1 and S100A13, which is a component of FGF1 export pathway. FGF1 export and acceleration of cell growth induced by dnCBF1 depend on SphK1. Similar to dnCBF1, dnMAML transfection induces FGF1 expression and release, and accelerates cell proliferation. The latter effect is strongly decreased in FGF1 null cells. We suggest that the regulation of FGF1 expression and release by CBF1-mediated Notch signaling can play an important role in tumor formation. PMID:21302306

  19. Hydrolysis Process of the Anticancer Agents Novel Non-classical trans-Platinum(Ⅱ) with Aliphatic Amines

    Institute of Scientific and Technical Information of China (English)

    YUAN Qing-Hui; ZHOU Li-Xin

    2007-01-01

    The hydrolysis process of the anticancer agents novel non-classical transplatinum( Ⅱ ) with aliphatic amines and the influence of solvent models therein have been studied by using hybrid density functional theory (B3LYP). In this study, the stepwise hydrolysis, trans[PtCl2(Am)(isopropylamine)] + 2H2O → trans-[Pt(Am)(isopropylamine)(OH2)2]2++ 2Cl-, was explored. Implicit solvent effects were incorporated through polarized continuum models. The stationary points on the potential energy surfaces for the first and second hydrolysis steps,proceeding via a general SN2 pathway, were fully optimized and characterized. It was found that the first hydrolysis reaction is easier than the second one and the hydrolysis of trans- [PtCl2-(isopropylamine)2] is the easiest in our studying systems. The result can assist in under- tanding the hydrolysis mechanism of trans-[PtCl2(Am)(isopropylamine)] and designing novel Pt-based anticancer drugs.

  20. Ultralow-dose dexamethasone to preserve endogenous cortisol stress response in nonclassical congenital adrenal hyperplasia: A new promising treatment

    NARCIS (Netherlands)

    D.C.M. van der Kaay (Danielle); E.L.T. van den Akker (Erica)

    2014-01-01

    textabstractIntroduction: Nonclassical congenital adrenal hyperplasia (CAH) is characterized by sufficient cortisol and aldosterone production at the cost of androgen overproduction. Hydrocortisone or dexamethasone in supraphysiological doses are current treatment; however, their downside is suppres

  1. Reproducibility of Psychological Experiments as a Problem of Post-Nonclassical Science

    Directory of Open Access Journals (Sweden)

    Vachkov I.V.,

    2016-04-01

    Full Text Available A fundamental project on reproducibility carried out in the USA by Brian Nosek in 2015 (the Reproducibility Project revealed a serious methodological problem in psychology: the issue of replication of psycho- logical experiments. Reproducibility has been traditionally perceived as one of the basic principles of the scientific method. However, methodological analysis of the modern post-nonclassical stage in the development of science suggests that this might be a bit too uncompromising as applied to psychology. It seems that the very criteria of scientific research need to be reconsidered with regard to the specifics of post-nonclassical science, and, as the authors put it, as a result, reproducibility might lose its key status or even be excluded at all. The reviewed problem and the proposed ways of coping with it are of high importance to research and practice in psychology as they define the strategies for organizing, conducting and evaluating experimental research.

  2. Non-classical Signature of Parametric Fluorescence and its Application in Metrology

    Directory of Open Access Journals (Sweden)

    Hamar M.

    2014-08-01

    Full Text Available The article provides a short theoretical background of what the non-classical light means. We applied the criterion for the existence of non-classical effects derived by C.T. Lee on parametric fluorescence. The criterion was originally derived for the study of two light beams with one mode per beam. We checked if the criterion is still working for two multimode beams of parametric down-conversion through numerical simulations. The theoretical results were tested by measurement of photon number statistics of twin beams emitted by nonlinear BBO crystal pumped by intense femtoseconds UV pulse. We used ICCD camera as the detector of photons in both beams. It appears that the criterion can be used for the measurement of the quantum efficiencies of the ICCD cameras.

  3. Transient thermal cracking associated with non-classical heat conduction in cylindrical coordinate system

    Institute of Scientific and Technical Information of China (English)

    Bao-Lin Wang

    2013-01-01

    This paper studies the fracture behavior of a thermoelastic cylinder subjected to a sudden temperature change on its outer surface within the framework of non-classical heat conduction.The heat conduction equation is solved by separation of variable technique.Closed form solution for the temperature field and the associated thermal stress are established.The critical parameter governing the level of the transient thermal stress is identified.Exact expression for the transient stress intensity factor is obtained for a crack in the cylinder.The difference between the non-classical solutions and the classical solution are discussed.It is found that the traditional classical heat conduction considerably underestimates the transient thermal stress and thermal stress intensity factor.

  4. Experimental detection of non-classical correlations in mixed state quantum computation

    CERN Document Server

    Passante, G; Trottier, D A; Laflamme, R

    2011-01-01

    We report on an experiment to detect non-classical correlations in a highly mixed state. The correlations are characterized by the quantum discord and are observed using four qubits in a liquid state nuclear magnetic resonance quantum information processor. The state analyzed is the output of a DQC1 computation, whose input is a single quantum bit accompanied by n maximally mixed qubits. This model of computation outperforms the best known classical algorithms, and although it contains vanishing entanglement it is known to have quantum correlations characterized by the quantum discord. This experiment detects non-vanishing quantum discord, ensuring the existence of non-classical correlations as measured by the quantum discord.

  5. Nonclassical correlations between single photons and phonons from a mechanical oscillator

    CERN Document Server

    Riedinger, Ralf; Norte, Richard A; Slater, Joshua A; Shang, Juying; Krause, Alexander G; Anant, Vikas; Aspelmeyer, Markus; Gröblacher, S

    2015-01-01

    Interfacing a single photon with another quantum system is a key capability in modern quantum information science. It allows quantum states of matter, such as spin states of atoms, atomic ensembles or solids, to be prepared and manipulated by photon counting and, in particular, to be distributed over long distances. Such light-matter interfaces have become crucial for fundamental tests of quantum physics as well as for realizations of quantum networks. Here we report nonclassical correlations between single photons and phonons -- the quanta of mechanical motion -- from a nanomechanical resonator. We implement a full quantum protocol involving initialization of the resonator in its quantum ground state of motion and subsequent generation and readout of correlated photon-phonon pairs. The observed violation of a Cauchy-Schwarz inequality is clear evidence for the nonclassical nature of the generated mechanical state. Our results show the availability of on-chip solid-state mechanical resonators as light-matter ...

  6. Role of non-classical MHC class I molecules in cancer immunosuppression

    Science.gov (United States)

    Kochan, Grazyna; Escors, David; Breckpot, Karine; Guerrero-Setas, David

    2013-01-01

    Growing neoplasms employ various mechanisms to evade immunosurveillance. The expression of non-classical MHC class I molecules by both immune and malignant cells in the tumor microenvironment constitute of the strategies used by tumors to circumvent the cytotoxic activity of effector cells of the immune system. The overexpression of HLA-G, -E, and -F is a common finding across a variety of malignancies. However, while the presence of HLA-G and HLA-E has been recently correlated with poor clinical outcome, information on the clinicopathological significance of HLA-F is limited. In the present review, we summarize studies on non-classical MHC class I molecules with special emphasis on their role in the modulation of anticancer immune responses. PMID:24482746

  7. Nonclassical phase-space trajectories for the damped harmonic quantum oscillator

    Energy Technology Data Exchange (ETDEWEB)

    Pachon, L.A. [Departamento de Fisica, Universidad Nacional de Colombia, Bogota D.C. (Colombia); Institut fuer Physik, Universitaet Augsburg, Universitaetsstrasse 1, D-86135 Augsburg (Germany); CeiBA - Complejidad, Bogota D.C. (Colombia); Ingold, G.-L., E-mail: gert.ingold@physik.uni-augsburg.de [Institut fuer Physik, Universitaet Augsburg, Universitaetsstrasse 1, D-86135 Augsburg (Germany); Dittrich, T. [Departamento de Fisica, Universidad Nacional de Colombia, Bogota D.C. (Colombia); CeiBA - Complejidad, Bogota D.C. (Colombia)

    2010-10-05

    Graphical abstract: The phase-space path-integral approach to the damped harmonic oscillator is analyzed beyond the Markovian approximation and the appearance of nonclassical trajectories is discussed. - Abstract: The phase-space path-integral approach to the damped harmonic oscillator is analyzed beyond the Markovian approximation. It is found that pairs of nonclassical trajectories contribute to the path-integral representation of the Wigner propagating function. Due to the linearity of the problem, the sum coordinate of a pair still satisfies the classical equation of motion. Furthermore, it is shown that the broadening of the Wigner propagating function of the damped oscillator arises due to the time-nonlocal interaction mediated by the heat bath.

  8. Nonclassical correlation between optical and microwave photons in a hybrid electro-optomechanical system

    Science.gov (United States)

    Xie, Hong; Chen, Xiang; Lin, Gongwei; Lin, Xiumin

    2016-10-01

    A scheme to correlate optical and microwave photons is proposed in a hybrid electro-optomechanical system, where mechanical resonator is coupled to both optical and microwave fields. Analytical and numerical simulation results show that the cross-correlation function between Stokes and anti-Stokes photons strongly violates the Cauchy-Schwarz inequality, which confirms the nonclassical correlation between the optical and microwave photons. It is worth noting that the nonclassical photon pairs with vast different wavelengths, which may be useful for quantum communication, are generated under the experimentally accessible weak coupling limit rather than single-photon strong coupling regime. In addition, the protocol provides a possible route to combine the respective advantages of optical photons, microwave photons, and phonons in a hybrid electro-optomechanical system.

  9. Nonclassical Riemann solvers and kinetic relations III: A nonconvex hyperbolic model for Van der Waals fluids

    Directory of Open Access Journals (Sweden)

    Philippe G. LeFloch

    2000-12-01

    Full Text Available This paper deals with the so-called p-system describing the dynamics of isothermal and compressible fluids. The constitutive equation is assumed to have the typical convexity/concavity properties of the van der Waals equation. We search for discontinuous solutions constrained by the associated mathematical entropy inequality. First, following a strategy proposed by Abeyaratne and Knowles and by Hayes and LeFloch, we describe here the whole family of nonclassical Riemann solutions for this model. Second, we supplement the set of equations with a kinetic relation for the propagation of nonclassical undercompressive shocks, and we arrive at a uniquely defined solution of the Riemann problem. We also prove that the solutions depend $L^1$-continuously upon their data. The main novelty of the present paper is the presence of two inflection points in the constitutive equation. The Riemann solver constructed here is relevant for fluids in which viscosity and capillarity effects are kept in balance.

  10. EFFECTS OF PARAMETRIC VARIATIONS ON SEISMIC ANALYSIS METHODS FOR NON-CLASSICALLY DAMPED COUPLED SYSTEMS

    Energy Technology Data Exchange (ETDEWEB)

    XU,J.; DEGRASSI,G.

    2000-04-02

    A comprehensive benchmark program was developed by Brookhaven National Laboratory (BNL) to perform an evaluation of state-of-the-art methods and computer programs for performing seismic analyses of coupled systems with non-classical damping. The program, which was sponsored by the US Nuclear Regulatory Commission (NRC), was designed to address various aspects of application and limitations of these state-of-the-art analysis methods to typical coupled nuclear power plant (NPP) structures with non-classical damping, and was carried out through analyses of a set of representative benchmark problems. One objective was to examine the applicability of various analysis methods to problems with different dynamic characteristics unique to coupled systems. The examination was performed using parametric variations for three simple benchmark models. This paper presents the comparisons and evaluation of the program participants' results to the BNL exact solutions for the applicable ranges of modeling dynamic characteristic parameters.

  11. Nonclassical properties of electronic states of aperiodic chains in a homogeneous electric field

    Science.gov (United States)

    Spisak, B. J.; Wołoszyn, M.

    2009-07-01

    The electronic energy levels of one-dimensional aperiodic systems driven by a homogeneous electric field are studied by means of a phase-space description based on the Wigner distribution function. The formulation provides physical insight into the quantum nature of the electronic states for the aperiodic systems generated by the Fibonacci and Thue-Morse sequences. The nonclassical parameter for electronic states is studied as a function of the magnitude of homogeneous electric field to achieve the main result of this work, which is to prove that the nonclassical properties of the electronic states in the aperiodic systems determine the transition probability between electronic states in the region of anticrossings. The localization properties of electronic states and the uncertainty product of momentum and position variables are also calculated as functions of the electric field.

  12. Nonclassical and Postnonclassical epistemology in Lev Vygotsky’s cultural-historical approach to clinical psychology

    OpenAIRE

    Zinchenko Y.P.; Pervichko E.I.

    2013-01-01

    The work presents historiographic and theoretical methodological study of establishment of fundamental theses of L.S. Vygotsky’s cultural-historical concept within the field of clinical psychology.We prove potency in application of contemporary philosophical concepts, which help distinguish between the types of scientific rationality (classical, nonclassical, and postnonclassical), for scientific reflection over the development of psychology and designation of paradigmatic status of cultural-...

  13. Analytical Study of Nonclassical Behaviour for a Disturbed Non-Degenerated Parameter Amplifier

    Institute of Scientific and Technical Information of China (English)

    PANG Qian-Jun

    2007-01-01

    We analytically discuss the nonclassical behaviour for a disturbed non-degenerated parameter amplifier.The thermal Glauber-Sudarshan diagonal presentation (GSP)function for the system is derived.The detailed analysis on the threshold temperatures of both the individual photon subsystem and the complete photon-photon complex is presented.The offect of the photon-photon interaction on the threshold temperature is observed.

  14. Deterministic generation of non-classical states of light using photon blockade

    CERN Document Server

    Faraon, Andrei; Vuckovic, Jelena

    2009-01-01

    The generation of non-classical states of light via photon blockade with time-modulated input is analyzed. We show that improved single photon statistics can be obtained by adequately choosing the parameters of the driving laser pulses. An alternative method, where the system is driven via a continuous wave laser and the frequency of the dipole is controlled (e.g. electrically) at very fast timescales is presented.

  15. The Non-Classical Boltzmann Equation, and Diffusion-Based Approximations to the Boltzmann Equation

    CERN Document Server

    Frank, Martin; Larsen, Edward W; Vasques, Richard

    2014-01-01

    We show that several diffusion-based approximations (classical diffusion or SP1, SP2, SP3) to the linear Boltzmann equation can (for an infinite, homogeneous medium) be represented exactly by a non-classical transport equation. As a consequence, we indicate a method to solve diffusion-based approximations to the Boltzmann equation via Monte Carlo, with only statistical errors - no truncation errors.

  16. The nonlinear squeezed one-photon states and their nonclassical properties

    Institute of Scientific and Technical Information of China (English)

    Wang Ji-Suo; Meng Xiang-Guo

    2007-01-01

    By virtue of the technique of integration within an ordered product (IWOP) of operators and the properties of the inverses of annihilation and creation operators of f-oscillator, this paper obtains two new types of squeezed operators and f-analogues of squeezed one-photon states, which are quite different from ones constructed by Song and Fan (Phys. Lett. A 294 (2002) 66). Subsequently, some nonclassical properties of the states are investigated in detail.

  17. NClassG+: A classifier for non-classically secreted Gram-positive bacterial proteins

    Directory of Open Access Journals (Sweden)

    Pino Camilo

    2011-01-01

    Full Text Available Abstract Background Most predictive methods currently available for the identification of protein secretion mechanisms have focused on classically secreted proteins. In fact, only two methods have been reported for predicting non-classically secreted proteins of Gram-positive bacteria. This study describes the implementation of a sequence-based classifier, denoted as NClassG+, for identifying non-classically secreted Gram-positive bacterial proteins. Results Several feature-based classifiers were trained using different sequence transformation vectors (frequencies, dipeptides, physicochemical factors and PSSM and Support Vector Machines (SVMs with Linear, Polynomial and Gaussian kernel functions. Nested k-fold cross-validation (CV was applied to select the best models, using the inner CV loop to tune the model parameters and the outer CV group to compute the error. The parameters and Kernel functions and the combinations between all possible feature vectors were optimized using grid search. Conclusions The final model was tested against an independent set not previously seen by the model, obtaining better predictive performance compared to SecretomeP V2.0 and SecretPV2.0 for the identification of non-classically secreted proteins. NClassG+ is freely available on the web at http://www.biolisi.unal.edu.co/web-servers/nclassgpositive/

  18. [A non-classical approach to medical practices: Michel Foucault and Actor-Network Theory].

    Science.gov (United States)

    Bińczyk, E

    2001-01-01

    The text presents an analysis of medical practices stemming from two sources: Michel Foucault's conception and the research of Annemarie Mol and John Law, representatives of a trend known as Actor-Network Theory. Both approaches reveal significant theoretical kinship: they can be successfully consigned to the framework of non-classical sociology of science. I initially refer to the cited conceptions as a version of non-classical sociology of medicine. The identity of non-classical sociology of medicine hinges on the fact that it undermines the possibility of objective definitions of disease, health and body. These are rather approached as variable social and historical phenomena, co-constituted by medical practices. To both Foucault and Mol the main object of interest was not medicine as such, but rather the network of medical practices. Mol and Law sketch a new theoretical perspective for the analysis of medical practices. They attempt to go beyond the dichotomous scheme of thinking about the human body as an object of medical research and the subject of private experience. Research on patients suffering blood-sugar deficiency provide the empirical background for the thesis of Actor-Network Theory representatives. Michel Foucault's conceptions are extremely critical of medical practices. The French researcher describes the processes of 'medicalising' Western society as the emergence of a new type of power. He attempts to sensitise the reader to the ethical dimension of the processes of medicalising society.

  19. Asymptotic decay rate of non-classical strain gradient Timoshenko micro-cantilevers by boundary feedback

    Energy Technology Data Exchange (ETDEWEB)

    Vatankhah, Ramin; Salarieh, Hassan; Alasty, Aria [Sharif University of Technology, Tehran (Iran, Islamic Republic of); Najafi, Ali [Shiraz Branch, Islamic Azad University, Shiraz (Iran, Islamic Republic of)

    2014-02-15

    In non-classical micro-beams, the strain energy of the system is obtained based on the non-classical continuum mechanics. This paper presents the problem of boundary control of a vibrating non-classical micro-cantilever Timoshenko beam to achieve the asymptotic decay rate of the closed loop system. For this aim, we need to establish the well- posedness of the governing partial differential equations (PDEs) of motion in presence of boundary feedbacks. A linear control law is constructed to suppress the system vibration. The control forces and moments consist of feedbacks of the velocities and spatial derivatives of them at tip of the micro-beam. To verify the effectiveness of the proposed boundary controllers, numerical simulations of the open loop and closed loop PDE models of the system are worked out using finite element method (FEM). New Timoshenko beam element stiffness and mass matrices are derived based on the strain gradient theory and verification of this new beam element is accomplished.

  20. Partial-measurement backaction and nonclassical weak values in a superconducting circuit.

    Science.gov (United States)

    Groen, J P; Ristè, D; Tornberg, L; Cramer, J; de Groot, P C; Picot, T; Johansson, G; DiCarlo, L

    2013-08-30

    We realize indirect partial measurement of a transmon qubit in circuit quantum electrodynamics by interaction with an ancilla qubit and projective ancilla measurement with a dedicated readout resonator. Accurate control of the interaction and ancilla measurement basis allows tailoring the measurement strength and operator. The tradeoff between measurement strength and qubit backaction is characterized through the distortion of a qubit Rabi oscillation imposed by ancilla measurement in different bases. Combining partial and projective qubit measurements, we provide the solid-state demonstration of the correspondence between a nonclassical weak value and the violation of a Leggett-Garg inequality.

  1. Trapped ions in the strong-excitation regime: Ion interferometry and nonclassical states

    Energy Technology Data Exchange (ETDEWEB)

    Poyatos, J.F.; Cirac, J.I. [Departamento de Fisica Aplicada, Universidad de Castilla-La Mancha, 13071 Ciudad Real (Spain); Blatt, R. [Institut fuer Experimental Physik, Universitaet Goettingen, 37073 Goettingen (Germany); Zoller, P. [Institut fuer Theoretische Physik, Universitaet Innsbruck, 6020 Innsbruck (Austria)

    1996-08-01

    The interaction of a trapped ion with a laser beam in the strong-excitation regime is analyzed. In this regime, a variety of nonclassical states of motion can be prepared either by using laser pulses of well defined area, or by an adiabatic passage scheme based on the variation of the laser frequency. We show how these states can be used to investigate fundamental properties of quantum mechanics. We also study possible applications of this system to build an ion interferometer. {copyright} {ital 1996 The American Physical Society.}

  2. Stabilization of nonclassical states of the radiation field in a cavity by reservoir engineering.

    Science.gov (United States)

    Sarlette, A; Raimond, J M; Brune, M; Rouchon, P

    2011-07-01

    We propose an engineered reservoir inducing the relaxation of a cavity field towards nonclassical states. It is made up of two-level atoms crossing the cavity one at a time. Each atom-cavity interaction is first dispersive, then resonant, then dispersive again. The reservoir pointer states are those produced by an effective Kerr Hamiltonian acting on a coherent field. We thereby stabilize squeezed states and quantum superpositions of multiple coherent components in a cavity having a finite damping time. This robust decoherence protection method could be implemented in state-of-the-art experiments.

  3. Finite-dimensional even and odd nonlinear pair coherent states and their some nonclassical properties

    Institute of Scientific and Technical Information of China (English)

    Meng Xiang-Guo; Wang Ji-Suo; Liu Tang-Kun

    2008-01-01

    In this paper a new class of finite-dimensional even and odd nonlinear pair coherent states(EONLPCSs),which can be realized via operating the superposed evolution operators D±(τ)on the state |q,0),is constructed,then their orthonormalized property,completeness relations and some nonclassical properties are discussed.It is shown that the finite-dimensional EONLPCSs possess normalization and completeness relations.Moreover,the finite-dimensional EONLPCSs exhibit remarkably different sub-Poissonian distributions and phase probability distributions for different values of parameters q,η and ξ.

  4. Blue Sky Catastrophe in Systems with Non-classical Relaxation Oscillations

    Directory of Open Access Journals (Sweden)

    S. D. Glyzin

    2015-01-01

    Full Text Available The feasibility of a known blue-sky bifurcation in a class of three-dimensional singularly perturbed systems of ordinary differential equations with one fast and two slow variables is studied. A characteristic property of the considered systems is that they permit so-called nonclassic relaxation oscillations, that is, oscillations with slow components asymptotically close to time-discontinuous functions and a δ-like fast component. Cases when blue-sky bifurcation leads to a relaxation cycle or stable two-dimensional torus are analyzed. Also the question of homoclinic structure emergence is considered.

  5. Non-classical solutions of a continuum model for rock descriptions

    Institute of Scientific and Technical Information of China (English)

    Mikhail A.Guzev

    2014-01-01

    The strain-gradient and non-Euclidean continuum theories are employed for construction of non-classical solutions of continuum models. The linear approximation of both models’ results in identical structures in terms of their kinematic and stress characteristics. The solutions obtained in this study exhibit a critical behaviour with respect to the external loading parameter. The conclusions are obtained based on an investigation of the solution for the scalar curvature in the non-Euclidean continuum theory. The proposed analysis enables us to use different theoretical approaches for description of rock critical behaviour under different loading conditions.

  6. An analysis of non-classical austenite-martensite interfaces in CuAlNi

    CERN Document Server

    Ball, J M; Seiner, H

    2011-01-01

    Ball and Carstensen theoretically investigated the possibility of the occurrence of non-classical austenite-martensite interfaces and studied the cubic-to-tetragonal case extensively. Here, we aim to present an analysis of such interfaces recently observed by Seiner et al. in CuAlNi single crystals, undergoing a cubic-to-orthorhombic transition. We show that they can be described by the non-linear elasticity model for martensitic transformations and we make some predictions regarding the volume fractions of the martensitic variants involved, as well as the habit plane normals.

  7. Generation of higher order nonclassical states via interaction of intense electromagnetic field with third order nonlinear medium

    CERN Document Server

    Pathak, A

    2006-01-01

    Interaction of intense laser beam with an inversion symmetric third order nonlinear medium is modeled as a quartic anharmonic oscillator. A first order operator solution of the model Hamiltonian is used to study the possibilities of generation of higher order nonclassical states. It is found that the higher order squeezed and higher order antibunched states can be produced by this interaction. It is also shown that the higher order nonclassical states may appear separately, i.e. a higher order antibunched state is not essentially higher order squeezed state and vice versa.

  8. Generation of non-classical correlated photon pairs via a ladder-type atomic configuration: theory and experiment.

    Science.gov (United States)

    Ding, Dong-Sheng; Zhou, Zhi-Yuan; Shi, Bao-Sen; Zou, Xu-Bo; Guo, Guang-Can

    2012-05-07

    We experimentally generate a non-classical correlated two-color photon pair at 780 and 1529.4 nm in a ladder-type configuration using a hot 85Rb atomic vapor with the production rate of ~10(7)/s. The non-classical correlation between these two photons is demonstrated by strong violation of Cauchy-Schwarz inequality by the factor R = 48 ± 12. Besides, we experimentally investigate the relations between the correlation and some important experimental parameters such as the single-photon detuning, the powers of pumps. We also make a theoretical analysis in detail and the theoretical predictions are in reasonable agreement with our experimental results.

  9. ON THE POLARIZATION OF CREATIVE CONSCIOUSNESS IN NON-CLASSICAL ERA OF RUSSIAN LITERATURE

    Directory of Open Access Journals (Sweden)

    Oleg Nikolaevich Sklyarov

    2014-10-01

    Full Text Available The article deals with the phenomenon of "branch" of the total flow of philosophical and aesthetic quest in Russian postsimbolism in the early 20th century and the implications of this polarization in the literary process in the following decades. Special attention is paid to the specifics of the non-classical consciousness, an important feature of which is the intention of the "targeting" of artistic expression. The main lines of development of Russian literature in the 20th century are briefly described. The subject of primary attention of the author are mental peculiarities, features of creative thinking inherited in individuals of every from ideological and artistic "vectors", forming a common paradigm of national literature in the non-classical era. The understanding the specifics of the "middle" line of creative research, defined by the concept of "neotraditionalism" becomes the center of the problem field in the article. In understanding and presentation of the essence of the neotraditional type of creative consciousness author moves into the mainstream, a paved by work of V.I. Tyupa, who proposed in the early 90s as the term itself, taken now adopted by many scientists and methodological principles of neotraditionalism identification as a special type of mental orientation in art. 

  10. Nonclassical Ly6C− Monocytes Drive the Development of Inflammatory Arthritis in Mice

    Directory of Open Access Journals (Sweden)

    Alexander V. Misharin

    2014-10-01

    Full Text Available Different subsets and/or polarized phenotypes of monocytes and macrophages may play distinct roles during the development and resolution of inflammation. Here, we demonstrate in a murine model of rheumatoid arthritis that nonclassical Ly6C− monocytes are required for the initiation and progression of sterile joint inflammation. Moreover, nonclassical Ly6C− monocytes differentiate into inflammatory macrophages (M1, which drive disease pathogenesis and display plasticity during the resolution phase. During the development of arthritis, these cells polarize toward an alternatively activated phenotype (M2, promoting the resolution of joint inflammation. The influx of Ly6C− monocytes and their subsequent classical and then alternative activation occurs without changes in synovial tissue-resident macrophages, which express markers of M2 polarization throughout the course of the arthritis and attenuate joint inflammation during the initiation phase. These data suggest that circulating Ly6C− monocytes recruited to the joint upon injury orchestrate the development and resolution of autoimmune joint inflammation.

  11. A non-classical Mindlin plate model incorporating microstructure, surface energy and foundation effects

    Science.gov (United States)

    Gao, X.-L.; Zhang, G. Y.

    2016-07-01

    A non-classical model for a Mindlin plate resting on an elastic foundation is developed in a general form using a modified couple stress theory, a surface elasticity theory and a two-parameter Winkler-Pasternak foundation model. It includes all five kinematic variables possible for a Mindlin plate. The equations of motion and the complete boundary conditions are obtained simultaneously through a variational formulation based on Hamilton's principle, and the microstructure, surface energy and foundation effects are treated in a unified manner. The newly developed model contains one material length-scale parameter to describe the microstructure effect, three surface elastic constants to account for the surface energy effect, and two foundation parameters to capture the foundation effect. The current non-classical plate model reduces to its classical elasticity-based counterpart when the microstructure, surface energy and foundation effects are all suppressed. In addition, the new model includes the Mindlin plate models considering the microstructure dependence or the surface energy effect or the foundation influence alone as special cases, recovers the Kirchhoff plate model incorporating the microstructure, surface energy and foundation effects, and degenerates to the Timoshenko beam model including the microstructure effect. To illustrate the new Mindlin plate model, the static bending and free vibration problems of a simply supported rectangular plate are analytically solved by directly applying the general formulae derived.

  12. The Heteronuclear Multiple-Quantum Correlation Experiment: Perspective from Classical Vectors, Nonclassical Vectors, and Product Operators

    Directory of Open Access Journals (Sweden)

    Karen de la Vega-Hernández

    2016-01-01

    Full Text Available It is usually accepted that most 2D-NMR experiments cannot be approached using classical models. Instructors argue that Product Operators (PO or density matrix formalisms are the only alternative to get insights into complex spin evolution for experiments involving Multiple-Quantum Coherence, such as the Heteronuclear Multiple-Quantum Correlation (HMQC technique. Nevertheless, in recent years, several contributions have been published to provide vectorial descriptions for the HMQC taking PO formalism as the starting point. In this work we provide a graphical representation of the HMQC experiment, taking the basic elements of Bloch’s vector model as building blocks. This description bears an intuitive and comfortable understanding of spin evolution during the pulse sequence, for those who are novice in 2D-NMR. Finally, this classical vectorial depiction is tested against the PO formalism and nonclassical vectors, conveying the didactic advantage of shedding light on a single phenomenon from different perspectives. This comparative approach could be useful to introduce PO and nonclassical vectors for advanced upper-division undergraduate and graduate education.

  13. Concrete damage diagnosed using the non-classical nonlinear acoustic method

    Institute of Scientific and Technical Information of China (English)

    Zhou Dao; Liu Xiao-Zhou; Gong Xiu-Fen; Nazarov V E; Ma Li

    2009-01-01

    It is known that the strength of concrete is seriously affected by damage and cracking. In this paper, six concrete samples under different damage levels are studied. The experimental results show a linear dependence of the resonance frequency shift on strain amplitude at the fundamental frequency, and approximate quadratic dependence of the am-plitudes of the second and third harmonics on strain amplitude at the fundamental frequency as well. In addition, the amplitude of the third harmonics is shown to increase with the increase of damage level, which is even higher than that of the second harmonics in samples with higher damage levels. These are three properties of non-classical nonlinear acoustics. The nonlinear parameters increase from 106 to 108 with damage level, and are more sensitive to the damage level of the concrete than the linear parameters obtained by using traditional acoustics methods. So, this method based on non-classical nonlinear acoustics may provide a better means of non-destructive testing (NDT) of concrete and other porous materials.

  14. Inability of the entropy vector method to certify nonclassicality in linelike causal structures

    Science.gov (United States)

    Weilenmann, Mirjam; Colbeck, Roger

    2016-10-01

    Bell's theorem shows that our intuitive understanding of causation must be overturned in light of quantum correlations. Nevertheless, quantum mechanics does not permit signaling and hence a notion of cause remains. Understanding this notion is not only important at a fundamental level, but also for technological applications such as key distribution and randomness expansion. It has recently been shown that a useful way to decide which classical causal structures could give rise to a given set of correlations is to use entropy vectors. These are vectors whose components are the entropies of all subsets of the observed variables in the causal structure. The entropy vector method employs causal relationships among the variables to restrict the set of possible entropy vectors. Here, we consider whether the same approach can lead to useful certificates of nonclassicality within a given causal structure. Surprisingly, we find that for a family of causal structures that includes the usual bipartite Bell structure they do not. For all members of this family, no function of the entropies of the observed variables gives such a certificate, in spite of the existence of nonclassical correlations. It is therefore necessary to look beyond entropy vectors to understand cause from a quantum perspective.

  15. Nonclassical properties and decoherence of fields in photon-added squeezing-enhanced thermal states

    Science.gov (United States)

    Wang, Zhen; Meng, Xiang-Guo; Li, Heng-Mei; Yuan, Hong-Chun

    2014-04-01

    We put forward the photon-added squeezing-enhanced thermal states (PASETS) theoretically by adding photon to the squeezed enhancing thermal states (SETS) repeatedly. Based on the normally ordered density operator of PASETS, we investigate the nonclassical behavior of the PASETS by evaluating, both analytically and numerically, Mandel's Q-parameter, photon-number distribution (PND), and Wigner function (WF). It is found that smaller squeezing parameter r and thermal photon number nc can lead to more chance of the appearance of sub-Poissonian statistics. And it is shown that the PND of PASETS exhibit more remarkable oscillations than that of SETS in stronger squeezing case. The WF exhibit partial negativity in phase space and the squeezing parameter r can result in both squeezing and rotating effect. By investigating the fidelity between PASETS and SETS shows that the fidelity tender to steady values in the high value of squeezing parameter or thermal photon number. In addition, the decoherence effect on the PASETS is examined by the time-evolution of the analytical WF in thermal channel. The results show that the PASETS shall lose nonclassicality and non-Gaussianity and reduce to classical states with Gaussian distribution after sufficient time interaction with the thermal noise. And larger photon-added number or thermal photon number shall render shorter decoherence time.

  16. A method for stochastic seismic response analysis of non-classically damped structures

    Institute of Scientific and Technical Information of China (English)

    徐清; 高存臣; 王君杰

    2004-01-01

    A method to calculate the stationary random response of a non-classically damped structure is proposed that features clearly-defined physical meaning and simple expression. The method is developed in the trequency domain. The expression of the proposed method consists of three terms, i.e., modal velocity response, modal displacement response, and coupled (between modal velocity and modal displacement response). Numerical results from the parametric study and three example structures reveal that the modal velocity response term and the coupled term are important to structural response estimates only for a dynamic system with a tuned mass damper. In typical cases, the modal displacement term can provide response estimates with satisfactory accuracy by itself, so that the modal velocity term and coupled term may be ignored without loss of accuracy. This is used to simplifv the response computation of non-classically damped structures. For the white noise excitation, three modal correlation coefficients m closed form are derived. To consider the modal velocity response term and the coupled term, a simplified approximation based on white noise excitation is developed for the case when the modal velocity response is important to the structural responses. Numerical results show that the approximate expression based on white noise excitation can provide structural responses with satisfactory accuracy.

  17. Local interaction simulation approach to modelling nonclassical, nonlinear elastic behavior in solids.

    Science.gov (United States)

    Scalerandi, Marco; Agostini, Valentina; Delsanto, Pier Paolo; Van Den Abeele, Koen; Johnson, Paul A

    2003-06-01

    Recent studies show that a broad category of materials share "nonclassical" nonlinear elastic behavior much different from "classical" (Landau-type) nonlinearity. Manifestations of "nonclassical" nonlinearity include stress-strain hysteresis and discrete memory in quasistatic experiments, and specific dependencies of the harmonic amplitudes with respect to the drive amplitude in dynamic wave experiments, which are remarkably different from those predicted by the classical theory. These materials have in common soft "bond" elements, where the elastic nonlinearity originates, contained in hard matter (e.g., a rock sample). The bond system normally comprises a small fraction of the total material volume, and can be localized (e.g., a crack in a solid) or distributed, as in a rock. In this paper a model is presented in which the soft elements are treated as hysteretic or reversible elastic units connected in a one-dimensional lattice to elastic elements (grains), which make up the hard matrix. Calculations are performed in the framework of the local interaction simulation approach (LISA). Experimental observations are well predicted by the model, which is now ready both for basic investigations about the physical origins of nonlinear elasticity and for applications to material damage diagnostics.

  18. An Approach to Some Non-Classical Eigenvalue Problems of Structural Dynamics

    Directory of Open Access Journals (Sweden)

    Sandi Horea

    2015-12-01

    Full Text Available Two main shortcomings of common formulations, encountered in the literature concerning the linear problems of structural dynamics are revealed: the implicit, not discussed, postulation, of the use of Kelvin – Voigt constitutive laws (which is often infirmed by experience and the calculation difficulties involved by the attempts to use other constitutive laws. In order to overcome these two categories of shortcomings, the use of the bilateral Laplace – Carson transformation is adopted. Instead of the dependence on time, t, of a certain function f (t, the dependence of its image f# (p on the complex parameter p = χ + iω (ω: circular frequency will occur. This leads to the formulation of associated non-classical eigenvalue problems. The basic relations satisfied by the eigenvalues λr#(p and the eigenvectors vr#(p of dynamic systems are examined (among other, the property of orthogonality of eigenvectors is replaced by the property of pseudo-orthogonality. The case of points p = p’, where multiple eigenvalues occur and where, as a rule, chains of principal vectors are to be considered, is discussed. An illustrative case, concerning a non-classical eigenvalue problem, is presented. Plots of variation along the ω axis, for the real and imaginary components of eigenvalues and eigenvectors, are presented. A brief final discussion closes the paper.

  19. High-accuracy acoustic detection of nonclassical component of material nonlinearity.

    Science.gov (United States)

    Haupert, Sylvain; Renaud, Guillaume; Rivière, Jacques; Talmant, Maryline; Johnson, Paul A; Laugier, Pascal

    2011-11-01

    The aim is to assess the nonclassical component of material nonlinearity in several classes of materials with weak, intermediate, and high nonlinear properties. In this contribution, an optimized nonlinear resonant ultrasound spectroscopy (NRUS) measuring and data processing protocol applied to small samples is described. The protocol is used to overcome the effects of environmental condition changes that take place during an experiment, and that may mask the intrinsic nonlinearity. External temperature fluctuation is identified as a primary source of measurement contamination. For instance, a variation of 0.1 °C produced a frequency variation of 0.01%, which is similar to the expected nonlinear frequency shift for weakly nonlinear materials. In order to overcome environmental effects, the reference frequency measurements are repeated before each excitation level and then used to compute nonlinear parameters. Using this approach, relative resonant frequency shifts of 10(-5) can be measured, which is below the limit of 10(-4) often considered as the limit of NRUS sensitivity under common experimental conditions. Due to enhanced sensitivity resulting from the correction procedure applied in this work, nonclassical nonlinearity in materials that before have been assumed to only be classically nonlinear in past work (steel, brass, and aluminum) is reported.

  20. Human yeast-specific CD8 T lymphocytes show a nonclassical effector molecule profile.

    Science.gov (United States)

    Breinig, Tanja; Scheller, Nicoletta; Glombitza, Birgit; Breinig, Frank; Meyerhans, Andreas

    2012-05-01

    Pathogenic yeast and fungi represent a major group of human pathogens. The consequences of infections are diverse and range from local, clinically uncomplicated mycosis of the skin to systemic, life-threatening sepsis. Despite extensive MHC class I-restricted frequencies of yeast-specific CD8 T lymphocytes in healthy individuals and the essential role of the cell-mediated immunity in controlling infections, the characteristics and defense mechanisms of antifungal effector cells are still unclear. Here, we describe the direct analysis of yeast-specific CD8 T lymphocytes in whole blood from healthy individuals. They show a unique, nonclassical phenotype expressing granulysin and granzyme K in lytic granules instead of the major effector molecules perforin and granzyme B. After stimulation in whole blood, yeast-specific CD8 T cells degranulated and, upon cultivation in the presence of IL-2, their granula were refilled with granulysin rather than with perforin and granzyme B. Moreover, yeast-specific stimulation through dendritic cells but not by yeast cells alone led to degranulation of the effector cells. As granulysin is the only effector molecule in lytic granules known to have antifungal properties, our data suggest yeast-specific CD8 T cells to be a nonclassical effector population whose antimicrobial effector machinery seems to be tailor-made for the efficient elimination of fungi as pathogens.

  1. Non-classical correlations between single photons and phonons from a mechanical oscillator

    Science.gov (United States)

    Riedinger, Ralf; Hong, Sungkun; Norte, Richard A.; Slater, Joshua A.; Shang, Juying; Krause, Alexander G.; Anant, Vikas; Aspelmeyer, Markus; Gröblacher, Simon

    2016-02-01

    Interfacing a single photon with another quantum system is a key capability in modern quantum information science. It allows quantum states of matter, such as spin states of atoms, atomic ensembles or solids, to be prepared and manipulated by photon counting and, in particular, to be distributed over long distances. Such light-matter interfaces have become crucial to fundamental tests of quantum physics and realizations of quantum networks. Here we report non-classical correlations between single photons and phonons—the quanta of mechanical motion—from a nanomechanical resonator. We implement a full quantum protocol involving initialization of the resonator in its quantum ground state of motion and subsequent generation and read-out of correlated photon-phonon pairs. The observed violation of a Cauchy-Schwarz inequality is clear evidence for the non-classical nature of the mechanical state generated. Our results demonstrate the availability of on-chip solid-state mechanical resonators as light-matter quantum interfaces. The performance we achieved will enable studies of macroscopic quantum phenomena as well as applications in quantum communication, as quantum memories and as quantum transducers.

  2. Effect of dielectric medium on the nonclassical properties of nonlinear sphere coherent states

    Directory of Open Access Journals (Sweden)

    E Amooghorban

    2014-04-01

    Full Text Available In order to investigate the effect of a medium with dissipation and dispersion and also the curvature of the physical space on the properties of the incident quantum states, we use the quantization of electromagnetic field based on phenomenological approach to obtain input-output relations between radiations on both sides of dielectric slab. By using these relations the fidelity, the Wigner function, and also the quantum correlation of the outgoing state through dielectric slab are obtained for a situation in which the rightward incident state is a nonlinear coherent state on a sphere and the leftward incident state is a vacuum state. Here, the incident states are considered monochromatic and the modeling of the medium is given by the Lorentz' model. Accordingly, we study nonclassical properties of the output states such as the quantum entanglement. It will be observed that the nonclassical properties of the outgoing states depend strongly on the optical property of the medium and also on the curvature of the physical state.

  3. Non-classical phenotypes of autoimmune hepatitis and advances in diagnosis and treatment

    Institute of Scientific and Technical Information of China (English)

    Albert J Czaja; Yusuf Bayraktar

    2009-01-01

    Non-classical manifestations of autoimmune hepatitis can delay diagnosis and treatment. Our aims were to describe the clinical phenotypes that can confound the diagnosis, detail scoring systems that can ensure their recognition, and outline advances in treatment that can improve their outcome. Prime source and review articles in English were selected through Medline from 1970-2008 and assimilated into personal libraries spanning 32 years. Acute severe or asymptomatic presentations and atypical histological findings,including centrilobular zone 3 necrosis and concurrent bile duct changes, are compatible with the diagnosis.Cholangiographic abnormalities may be present in children and adults with the disease, and autoimmune hepatitis must be considered in patients without autoantibodies or with antimitochondrial antibodies and no other cholestatic features. Asymptomatic patients frequently become symptomatic; mild disease can progress; and there are no confident indices that justify withholding treatment. Two diagnostic scoring systems with complementary virtues have been developed to evaluate patients with confusing features. Normal liver tests and tissue constitute the optimal end point of treatment, and the first relapse is an indication for longterm azathioprine therapy. Cyclosporine, tacrolimus and mycophenolate mofetil are promising salvage therapies, and budesonide with azathioprine may be a superior frontline treatment. We conclude that the non-classical phenotypes of autoimmune hepatitis can be recognized promptly, diagnosed accurately, and treated effectively.

  4. New fundamental evidence of non-classical structure in the combination of natural concepts.

    Science.gov (United States)

    Aerts, D; Sozzo, S; Veloz, T

    2016-01-13

    We recently performed cognitive experiments on conjunctions and negations of two concepts with the aim of investigating the combination problem of concepts. Our experiments confirmed the deviations (conceptual vagueness, underextension, overextension etc.) from the rules of classical (fuzzy) logic and probability theory observed by several scholars in concept theory, while our data were successfully modelled in a quantum-theoretic framework developed by ourselves. In this paper, we isolate a new, very stable and systematic pattern of violation of classicality that occurs in concept combinations. In addition, the strength and regularity of this non-classical effect leads us to believe that it occurs at a more fundamental level than the deviations observed up to now. It is our opinion that we have identified a deep non-classical mechanism determining not only how concepts are combined but, rather, how they are formed. We show that this effect can be faithfully modelled in a two-sector Fock space structure, and that it can be exactly explained by assuming that human thought is the superposition of two processes, a 'logical reasoning', guided by 'logic', and a 'conceptual reasoning', guided by 'emergence', and that the latter generally prevails over the former. All these findings provide new fundamental support to our quantum-theoretic approach to human cognition.

  5. Aurora A phosphorylates MCAK to control ran-dependent spindle bipolarity.

    Science.gov (United States)

    Zhang, Xin; Ems-McClung, Stephanie C; Walczak, Claire E

    2008-07-01

    During mitosis, mitotic centromere-associated kinesin (MCAK) localizes to chromatin/kinetochores, a cytoplasmic pool, and spindle poles. Its localization and activity in the chromatin region are regulated by Aurora B kinase; however, how the cytoplasmic- and pole-localized MCAK are regulated is currently not clear. In this study, we used Xenopus egg extracts to form spindles in the absence of chromatin and centrosomes and found that MCAK localization and activity are tightly regulated by Aurora A. This regulation is important to focus microtubules at aster centers and to facilitate the transition from asters to bipolar spindles. In particular, we found that MCAK colocalized with NuMA and XMAP215 at the center of Ran asters where its activity is regulated by Aurora A-dependent phosphorylation of S196, which contributes to proper pole focusing. In addition, we found that MCAK localization at spindle poles was regulated through another Aurora A phosphorylation site (S719), which positively enhances bipolar spindle formation. This is the first study that clearly defines a role for MCAK at the spindle poles as well as identifies another key Aurora A substrate that contributes to spindle bipolarity.

  6. Triggering signaling pathways using F-actin self-organization.

    Science.gov (United States)

    Colin, A; Bonnemay, L; Gayrard, C; Gautier, J; Gueroui, Z

    2016-10-04

    The spatiotemporal organization of proteins within cells is essential for cell fate behavior. Although it is known that the cytoskeleton is vital for numerous cellular functions, it remains unclear how cytoskeletal activity can shape and control signaling pathways in space and time throughout the cell cytoplasm. Here we show that F-actin self-organization can trigger signaling pathways by engineering two novel properties of the microfilament self-organization: (1) the confinement of signaling proteins and (2) their scaffolding along actin polymers. Using in vitro reconstitutions of cellular functions, we found that both the confinement of nanoparticle-based signaling platforms powered by F-actin contractility and the scaffolding of engineered signaling proteins along actin microfilaments can drive a signaling switch. Using Ran-dependent microtubule nucleation, we found that F-actin dynamics promotes the robust assembly of microtubules. Our in vitro assay is a first step towards the development of novel bottom-up strategies to decipher the interplay between cytoskeleton spatial organization and signaling pathway activity.

  7. Structural Insight into Archaic and Alternative Chaperone-Usher Pathways Reveals a Novel Mechanism of Pilus Biogenesis

    NARCIS (Netherlands)

    Pakharukova, Natalia; Garnett, J.A.; Tuittila, Minna; Paavilainen, Sari; Diallo, Mamou; Xu, Yingqi; Matthews, S.J.; Zavialov, A.V.

    2015-01-01

    Gram-negative pathogens express fibrous adhesive organelles that mediate targeting to sites of infection. The major class of these organelles is assembled via the classical, alternative and archaic chaperone-usher pathways. Although non-classical systems share a wider phylogenetic distribution an

  8. [Successful treatment and pregnancy in a women with the non-classic form of congenital adrenal hyperplasia

    NARCIS (Netherlands)

    Akker, E. van den; Stikkelbroeck, M.M.L.; Menheere, P.P.C.A.; Roumen, F.J.M.E.; Otten, B.J.

    2002-01-01

    In an 18-year-old woman non-classic 21-hydroxylase deficiency was diagnosed and dexamethasone treatment was instituted. Ten years later, she became pregnant for the first time; at 37 weeks unexpected intrauterine foetal death was found to have occurred. A second pregnancy ended with a spontaneous

  9. Interferometry with non-classical motional states of a Bose-Einstein condensate

    Science.gov (United States)

    van Frank, S.; Negretti, A.; Berrada, T.; Bücker, R.; Montangero, S.; Schaff, J.-F.; Schumm, T.; Calarco, T.; Schmiedmayer, J.

    2014-05-01

    The Ramsey interferometer is a prime example of precise control at the quantum level. It is usually implemented using internal states of atoms, molecules or ions, for which powerful manipulation procedures are now available. Whether it is possible to control external degrees of freedom of more complex, interacting many-body systems at this level remained an open question. Here we demonstrate a two-pulse Ramsey-type interferometer for non-classical motional states of a Bose-Einstein condensate in an anharmonic trap. The control sequences used to manipulate the condensate wavefunction are obtained from optimal control theory and are directly optimized to maximize the interferometric contrast. They permit a fast manipulation of the atomic ensemble compared to the intrinsic decay processes and many-body dephasing effects. This allows us to reach an interferometric contrast of 92% in the experimental implementation.

  10. Driving linear systems towards non-classical states with the help of noise

    CERN Document Server

    Genoni, Marco G; Serafini, Alessio

    2012-01-01

    We study the possibility of taking bosonic systems subject to quadratic Hamiltonians and a noisy thermal environment to non-classical stationary states by weak Gaussian measurements and conditioned linear driving. We derive general analytical upper bounds for the single mode squeezing and multimode entanglement at steady state, depending only on the Hamiltonian parameters and on the number of thermal excitations of the bath. Our findings show that, rather surprisingly, larger number of thermal excitations in the bath allow for larger steady-state squeezing and entanglement if the efficiency of the Gaussian measurements conditioning the feedback loop is high enough. Such efficiencies are included in our exact treatment, which allows us to determine efficiency thresholds for the noise-enhancement of quantum resources to take place.

  11. Non-classical diffusion model for heat and mass transfer in laser drying

    Institute of Scientific and Technical Information of China (English)

    Xiulan Huai; Guoxiang Wang; Renqiu Jiang; Bin Li

    2004-01-01

    A numerical analysis of the laser drying process by employing a generalized, Maxwell-Cattaneo equation to treat both heat and mass transfer was presented. Calculations were performed to illustrate the non-classical transport of heat and moisture. The effect of the heat flux density and the initial moisture content on water removal was also investigated. The results indicate that the nonequilibrium mass diffusion plays an important role during the very early stages of moisture removal, especially at the surface of the medium. Away from the surface, the non-Fickian model shows a delay in the reduction of the moisture content. The calculation resuits also show that the initial moisture content of the medium has a considerable effect on water removal.

  12. Non-classical crystallization of thin films and nanostructures in CVD and PVD processes

    CERN Document Server

    Hwang, Nong Moon

    2016-01-01

    This book provides a comprehensive introduction to a recently-developed approach to the growth mechanism of thin films and nanostructures via chemical vapour deposition (CVD). Starting from the underlying principles of the low pressure synthesis of diamond films, it is shown that diamond growth occurs not by individual atoms but by charged nanoparticles. This newly-discovered growth mechanism turns out to be general to many CVD and some physical vapor deposition (PVD) processes. This non-classical crystallization is a new paradigm of crystal growth, with active research taking place on growth in solution, especially in biomineralization processes. Established understanding of the growth of thin films and nanostructures is based around processes involving individual atoms or molecules. According to the author’s research over the last two decades, however, the generation of charged gas phase nuclei is shown to be the rule rather than the exception in the CVD process, and charged gas phase nuclei are actively ...

  13. Non-classical photon correlation in a two-dimensional photonic lattice

    CERN Document Server

    Gao, Jun; Lin, Xiao-Feng; Jiao, Zhi-Qiang; Feng, Zhen; Zhou, Zheng; Gao, Zhen-Wei; Xu, Xiao-Yun; Chen, Yuan; Tang, Hao; Jin, Xian-Min

    2016-01-01

    Quantum interference and quantum correlation, as two main features of quantum optics, play an essential role in quantum information applications, such as multi-particle quantum walk and boson sampling. While many experimental demonstrations have been done in one-dimensional waveguide arrays, it remains unexplored in higher dimensions due to tight requirement of manipulating and detecting photons in large-scale. Here, we experimentally observe non-classical correlation of two identical photons in a fully coupled two-dimensional structure, i.e. photonic lattice manufactured by three-dimensional femtosecond laser writing. Photon interference consists of 36 Hong-Ou-Mandel interference and 9 bunching. The overlap between measured and simulated distribution is up to $0.890\\pm0.001$. Clear photon correlation is observed in the two-dimensional photonic lattice. Combining with controllably engineered disorder, our results open new perspectives towards large-scale implementation of quantum simulation on integrated phot...

  14. Universality of Nonclassical Nonlinearity Applications to Non-Destructive Evaluations and Ultrasonic

    CERN Document Server

    Delsanto, Pier Paolo

    2006-01-01

    This book comes as a result of the research work developed in the framework of two international projects: the European Science Foundation supported program NATEMIS (Nonlinear Acoustic Techniques for Micro-Scale Damage Diagnostics) and a Los Alamos-based international network. The main topics of both the programs and the book cover the phenomenology, theory and applications of Nonclassical Nonlinearity (NCNL). NCNL techniques have been found in recent years to be extremely powerful (up to 1000 times more than the corresponding linear techniques) in a wide range of applications, including Material Characterization, Ultrasonics, Geophysics and Maintenance and Restoration of artifacts. These techniques are being adopted as the main inspection and research tool in another European program: AERONEWS (Health monitoring of aircraft by nonlinear elastic wave propagation). In the future, the proposed Universality of NCNL is expected to extend the range of applications to numerous other fields and scientific discipline...

  15. A case of androgen-secreting adrenal carcinoma with non-classical congenital adrenal hyperplasia

    Directory of Open Access Journals (Sweden)

    Tarun Varma

    2013-01-01

    Full Text Available Androgen excess is one of the most common and disturbing endocrine disorder of reproductive-aged women, affecting approximately 7% of this population Androgen excess results in the development of androgenic features in the women affected, with the development of hirsutism, androgenic alopecia, ovulatory dysfunction, and, if extreme, even virilization and masculinization. Adrenocortical carcinoma (ACC is a rare malignancy accounting for 0.02% of all annual cancers reported. About 60% are functional tumors secreting hormones, with its consequent clinical manifestations, the Cushing′s syndrome due to cortisone, virilization due to androgens, feminization due to estrogens, or hypertension due to aldosterone. Adrenal tumors that secrete androgens exclusively are extremely rare. Here, we present a rare case of androgen-secreting adrenocortical carcinoma with non-classical congenital adrenal hyperplasia.

  16. Electro-mechanical engineering of non-classical photon emissions from single quantum dots

    Energy Technology Data Exchange (ETDEWEB)

    Hoefer, Bianca; Zallo, Eugenio; Zhang, Jiaxiang; Ding, Fei; Schmidt, Oliver G. [Institute for Integrative Nanosciences, IFW-Dresden, Helmholtzstrasse 20, D-01069 Dresden (Germany); Trotta, Rinaldo; Rastelli, Armando [Institute of Semiconductor and Solid State Physics, Johannes Kepler University Linz, Altenbergerstrasse 69, A-4040 Linz (Austria)

    2014-07-01

    Indistinguishable photons and entangled photon pairs are the key elements for quantum information applications, for example, building a quantum repeater. Self-assembled semiconductor quantum dots (QDs) are promising candidates for the creation of such non-classical photon emissions, and offer the possibility to be integrated into solid state devices. However, due to the random nature of the self-assembled growth process, post-growth treatments are required to engineer the exciton state in the QDs (e.g. energies, exciton lifetimes, and fine structure splittings). In this work, we study the electro-mechanical engineering of the exciton lifetime, emission energy in the QDs, with the aim to produce single photons with higher indistinguishability. Also we present a recent experimental study on the statistical properties of fine structure splittings in the QD ensemble, in order to gain a deeper understanding of how to generate entangled photon pairs using semiconductor QDs.

  17. Signatures of nonlinear optomechanics and engineering of nonclassical mechanical steady states

    Science.gov (United States)

    Borkje, Kjetil

    2013-03-01

    Motivated by recent improvements in coupling strength between light and mechanical motion, we study the strong coupling regime of cavity optomechanics theoretically. We focus on the regime where the optomechanical coupling rate is still small compared to the mechanical resonance frequency, but where the mechanically induced Kerr nonlinearity is significant. The response of the system to an optical drive is characterized. The average photon number in the cavity as a function of drive detuning can feature several peaks due to multi-photon transitions. Furthermore, we show that by optically driving the system at multiple frequencies, multi-photon transitions can facilitate the engineering of nonclassical steady states of the mechanical oscillator. The author acknowledges financial support from The Danish Council for Independent Research under the Sapere Aude program.

  18. Nonclassical light in coupled optical systems: anomalous power distribution, Fock space dynamics and supersymmetry

    CERN Document Server

    El-Ganainy, Ramy; Christodoulides, Demetrios N

    2013-01-01

    We investigate the dynamics of nonclassical states of light in coupled optical structures and we demonstrate a number of intriguing features associated with such arrangements. By diagonalizing the system's Hamiltonian, we show that these geometries can support eigenstates having anomalous optical intensity distribution with no classical counterpart. These features may provide new avenues towards manipulating light flow at the quantum level. By projecting the Hamiltonian operator on Hilbert subspaces spanning different numbers of photon excitations, we demonstrate that processes such as coherent transport, state localization and surface Bloch oscillations can take place in Fock space. Furthermore, we show that Hamiltonian representations of Fock space manifolds differing by one photon obey a discrete supersymmetry relation

  19. Continuous-wave non-classical light with GHz squeezing bandwidth

    CERN Document Server

    Ast, Stefan; Mehmet, Moritz; Steinlechner, Sebastian; Eberle, Tobias; Schnabel, Roman

    2012-01-01

    Squeezed states can be employed for entanglement-based continuous-variable quantum key distribution, where the secure key rate is proportional to the bandwidth of the squeezing. We produced a non-classical continuous-wave laser field at the telecommunication wavelength of 1550 nm, which showed squeezing over a bandwidth of more than 2 GHz. The experimental setup used parametric down-conversion via a periodically poled potassium titanyl phosphate crystal (PPKTP). We did not use any resonant enhancement for the funda- mental wavelength, which should in principle allow a production of squeezed light over the full phase-matching bandwidth of several nanometers. We measured the squeezing to be up to 0.3 dB below the vacuum noise from 50 MHz to 2 GHz limited by the measuring bandwidth of the homodyne detector. The squeezing strength was possibly limited by thermal lensing inside the non-linear crystal.

  20. Non-classical crystallization of silicon thin films during hot wire chemical vapor deposition

    Science.gov (United States)

    Jung, Jae-Soo; Lee, Sang-Hoon; Kim, Da-Seul; Kim, Kun-Su; Park, Soon-Won; Hwang, Nong-Moon

    2017-01-01

    The deposition behavior of silicon films by hot wire chemical vapor deposition (HWCVD) was approached by non-classical crystallization, where the building block of deposition is a nanoparticle generated in the gas phase of the reactor. The puzzling phenomenon of the formation of an amorphous incubation layer on glass could be explained by the liquid-like property of small charged nanoparticles (CNPs), which are generated in the initial stage of the HWCVD process. Using the liquid-like property of small CNPs, homo-epitaxial growth as thick as 150 nm could be successfully grown on a silicon wafer at 600 °C under the processing condition where CNPs as small as possible could be supplied steadily by a cyclic process which periodically resets the process. The size of CNPs turned out to be an important parameter in the microstructure evolution of thin films.

  1. A nonclassical symbolic theory of working memory, mental computations, and mental set

    CERN Document Server

    Eliashberg, Victor

    2009-01-01

    The paper tackles four basic questions associated with human brain as a learning system. How can the brain learn to (1) mentally simulate different external memory aids, (2) perform, in principle, any mental computations using imaginary memory aids, (3) recall the real sensory and motor events and synthesize a combinatorial number of imaginary events, (4) dynamically change its mental set to match a combinatorial number of contexts? We propose a uniform answer to (1)-(4) based on the general postulate that the human neocortex processes symbolic information in a "nonclassical" way. Instead of manipulating symbols in a read/write memory, as the classical symbolic systems do, it manipulates the states of dynamical memory representing different temporary attributes of immovable symbolic structures stored in a long-term memory. The approach is formalized as the concept of E-machine. Intuitively, an E-machine is a system that deals mainly with characteristic functions representing subsets of memory pointers rather ...

  2. Chronic lymphocytic leukemia cells diversify and differentiate in vivo via a nonclassical Th1-dependent, Bcl-6–deficient process

    Science.gov (United States)

    Patten, Piers E.M.; Ferrer, Gerardo; Chen, Shih-Shih; Simone, Rita; Marsilio, Sonia; Yan, Xiao-Jie; Gitto, Zachary; Yuan, Chaohui; Kolitz, Jonathan E.; Barrientos, Jacqueline; Allen, Steven L.; Rai, Kanti R.; MacCarthy, Thomas; Chu, Charles C.

    2016-01-01

    Xenografting primary tumor cells allows modeling of the heterogeneous natures of malignant diseases and the influences of the tissue microenvironment. Here, we demonstrate that xenografting primary chronic lymphocytic leukemia (CLL) B lymphocytes with activated autologous T cells into alymphoid mice results in considerable CLL B cell division and sizable T cell expansion. Nevertheless, most/all CD5+CD19+ cells are eventually lost, due in part to differentiation into antibody-secreting plasmablasts/plasma cells. CLL B cell differentiation is associated with isotype class switching and development of new IGHV-D-J mutations and occurs via an activation-induced deaminase-dependent pathway that upregulates IRF4 and Blimp-1 without appreciable levels of the expected Bcl-6. These processes were induced in IGHV-unmutated and IGHV-mutated clones by Th1-polarized T-bet+ T cells, not classical T follicular helper (Tfh) cells. Thus, the block in B cell maturation, defects in T cell action, and absence of antigen-receptor diversification, which are often cardinal characteristics of CLL, are not inherent but imposed by external signals and the microenvironment. Although these activities are not dominant features in human CLL, each occurs in tissue proliferation centers where the mechanisms responsible for clonal evolution operate. Thus, in this setting, CLL B cell diversification and differentiation develop by a nonclassical germinal center–like reaction that might reflect the cell of origin of this leukemia. PMID:27158669

  3. Qubit-oscillator systems in the ultrastrong-coupling regime and their potential for preparing nonclassical states

    Science.gov (United States)

    Nori, Franco; Ashhab, Sahel

    2011-03-01

    We consider a system composed of a two-level system (i.e. a qubit) and a harmonic oscillator in the ultrastrong-coupling regime, where the coupling strength is comparable to the qubit and oscillator energy scales. We explore the possibility of preparing nonclassical states in this system, especially in the ground state of the combined system. The nonclassical states that we consider include squeezed states, Schrodinger-cat states and entangled states. We also analyze the nature of the change in the ground state as the coupling strength is increased, going from a separable ground state in the absence of coupling to a highly entangled ground state in the case of very strong coupling. Reference: S. Ashhab and F. Nori, Phys. Rev. A 81, 042311 (2010). We thank support from DARPA, AFOSR, NSA, LPS, ARO, NSF, MEXT, JSPS, FIRST, and JST.

  4. Non-classical continuum theory for solids incorporating internal rotations and rotations of Cosserat theories

    Science.gov (United States)

    Surana, K. S.; Joy, A. D.; Reddy, J. N.

    2017-03-01

    This paper presents a non-classical continuum theory in Lagrangian description for solids in which the conservation and the balance laws are derived by incorporating both the internal rotations arising from the Jacobian of deformation and the rotations of Cosserat theories at a material point. In particular, in this non-classical continuum theory, we have (i) the usual displacements ( ±b \\varvec{u}) and (ii) three internal rotations ({}_i ±b \\varvec{Θ}) about the axes of a triad whose axes are parallel to the x-frame arising from the Jacobian of deformation (which are completely defined by the skew-symmetric part of the Jacobian of deformation), and (iii) three additional rotations ({}_e ±b \\varvec{Θ}) about the axes of the same triad located at each material point as additional three degrees of freedom referred to as Cosserat rotations. This gives rise to ±b \\varvec{u} and {}_e ±b \\varvec{{Θ} as six degrees of freedom at a material point. The internal rotations ({}_i ±b \\varvec{Θ}), often neglected in classical continuum mechanics, exist in all deforming solid continua as these are due to Jacobian of deformation. When the internal rotations {}_i ±b \\varvec{Θ} are resisted by the deforming matter, conjugate moment tensor arises that together with {}_i ±b \\varvec{Θ} may result in energy storage and/or dissipation, which must be accounted for in the conservation and the balance laws. The Cosserat rotations {}_e ±b \\varvec{Θ} also result in conjugate moment tensor which, together with {}_e ±b \\varvec{Θ}, may also result in energy storage and/or dissipation. The main focus of the paper is a consistent derivation of conservation and balance laws that incorporate aforementioned physics and associated constitutive theories for thermoelastic solids. The mathematical model derived here has closure, and the constitutive theories derived using two alternate approaches are in agreement with each other as well as with the condition resulting from the

  5. Detection of non-classical space-time correlations with a novel type of single-photon camera

    CERN Document Server

    Just, Felix; Cavanna, Andrea; Michel, Thilo; Gleixner, Thomas; Taheri, Michael; Vallerga, John; Campbell, Michael; Tick, Timo; Anton, Gisela; Chekhova, Maria V; Leuchs, Gerd

    2014-01-01

    During the last decades, multi-pixel detectors have been developed capable of registering single photons. The newly developed Hybrid Photon Detector camera has a remarkable property that it has not only spatial but also temporal resolution. In this work, we use this device for the detection of non-classical light from spontaneous parametric down-conversion and use two-photon correlations for the absolute calibration of its quantum efficiency.

  6. Influence of Intrinsic Decoherence on Nonclassical Effects of System of a Three-Level Atom in Ξ Configuration

    Institute of Scientific and Technical Information of China (English)

    XU Jing-Bo; ZOU Xu-Bo; GAO Xiao-Chun; FU Jian

    2004-01-01

    With the help of an SU(3) dynamical algebraic structure, we find an exact solution of the Milburn equation for the system of a three-level atom in the Ξ configuration interacting with one quantized field mode with arbitrary detuning. The exact solution is then used to discuss the influence of the intrinsic decoherence on the nonclassical properties of the system, such as collapes and revivals of the atomic populations, oscillations of the photon number distribution, and squeezing of the radiation field.

  7. Influence of Intrinsic Decoherence on Nonclassical Effects of System of a Three-LevelAtom in [1] Configuration

    Institute of Scientific and Technical Information of China (English)

    XUJing-Bo; ZOUXu-Bo; GAOXiao-Chun; FUJian

    2004-01-01

    With the help of an SU(3) dynamicalalgebraic structure, we ~nd an exact solutionof the Milburn equationfor the system of a three-levelatom in the [1] configuration interacting with one quantized field mode with arbitrary detuning ,The exact solution is then used to discuss the influence of the intrinsic decoherence on the nonclassical properties of the system,such as collapes and revivals of the atomic populations,oscillations of the photon number distribution,and squeezing of the radiation field.

  8. Non-Classical C–H···X Hydrogen Bonding and Its Role in Asymmetric Organocatalysis

    KAUST Repository

    Ajitha, Manjaly John

    2016-08-17

    Non-classical hydrogen bonds (NCHBs) have attracted significant interest in the past decade particularly because of their important role in asymmetric catalytic systems. These weak interactions (< 4 kcal/mol) offer much flexibility in the preorganization of molecular entities required to achieve high enantioselectivity. Herein, we review some recent important organocatalytic asymmetric reactions where a NCHB serves as a critical factor in determining the stereoselectivity.

  9. Non-classical neutron beams for fundamental and solid state research

    Indian Academy of Sciences (India)

    H Rauch

    2008-10-01

    The curious dual nature of the neutron, sometimes a particle, sometimes a wave, is wonderfully manifested in the various non-local interference and quantum contextuality effects observed in neutron interferometry. Non-classical states may become useful for novel fundamental and solid state research. Here we discuss unavoidable quantum losses as they appear in neutron phase-echo and spin rotation experiments and we show how entanglement effects in a single particle system demonstrate quantum contextuality. In all cases of interactions, parasitic beams are produced which cannot be recombined completely with the original beam. This means that a complete reconstruction of the original state would, in principle, be impossible which causes a kind of intrinsic irreversibility. Even small interaction potentials can have huge effects when they are applied in quantum Zeno-like experiments. Recently, it has been shown that an entanglement between external and internal degrees of freedom exists even in single particle systems. This contextuality phenomenon also shows that a quantum system carries much more information than usually extracted. The path towards advanced neutron quantum optics will be discussed.

  10. Linear problem of the shock wave disturbance in a non-classical case

    Science.gov (United States)

    Semenko, Evgeny V.

    2017-06-01

    A linear problem of the shock wave disturbance for a special (non-classical) case, where both pre-shock and post-shock flows are subsonic, is considered. The phase transition for the van der Waals gas is an example of this problem. Isentropic solutions are constructed. In addition, the stability of the problem is investigated and the known result is approved: the only neutral stability case occurs here. A strictly algebraic representation of the solution in the plane of the Fourier transform is obtained. This representation allows the solution to be studied both analytically and numerically. In this way, any solution can be decomposed into a sum of acoustic and vorticity waves and into a sum of initial (generated by initial perturbations), transmitted (through the shock) and reflected (from the shock) waves. Thus, the wave incidence/refraction/reflection is investigated. A principal difference of the refraction/reflection from the classical case is found, namely, the waves generated by initial pre-shock perturbations not only pass through the shock (i.e., generate post-shock transmitted waves) but also are reflected from it (i.e., generate pre-shock reflected waves). In turn, the waves generated by the initial post-shock perturbation are not only reflected from the shock (generate post-shock reflected waves) but also pass through it (generate pre-shock transmitted waves).

  11. A unified treatment of nonclassical nonlinear effects in the propagation of ultrasound in heterogeneous media.

    Science.gov (United States)

    Paolo Delsanto, Pier; Hirsekorn, Sigrun

    2004-04-01

    Recent experiments on rocks and other materials, such as soil, cement, concrete and damaged elastic materials, have led to the discovery of nonlinear (NL) hysteretic effects in their elastic behaviour. These observations suggest the existence of a NL mesoscopic elasticity universality class, to which all the aforementioned materials belong. The purpose of the present contribution is to search for the basic mathematical roots for nonclassical nonlinearity, in order to explain its universality, classify it and correlate it with the underlying meso- or microscopic interaction mechanisms. In our discussions we explicitly consider two quite different kinds of specimens: a two-bonded-elements structure and a thin multigrained bar. It is remarkable that, although the former includes only one interface and the latter very many interstices, the same "interaction box" formalism can be applied to both. Another important result of the proposed formalism is that the spectral contents of an arbitrary system for any input amplitude may be predicted, under certain assumptions, from the result of a single experiment at a higher amplitude.

  12. Does Wearing Textured Insoles during Non-class Time Improve Proprioception in Professional Dancers?

    Science.gov (United States)

    Steinberg, N; Tirosh, O; Adams, R; Karin, J; Waddington, G

    2015-11-01

    This study sought to determine whether textured insoles inserted in the sports shoes of young dancers improved their inversion and eversion ankle movement discrimination. 26 ballet dancers (14 female, 12 male) from the Australian Ballet School, ages 14-19 years, were divided into 2 groups according to sex and class levels. During the first 4 weeks, the first intervention group (GRP1) was asked to wear textured insoles in their sports shoes during non-class periods, and the second intervention group (GRP2) followed standard practice. In the next 4 weeks, GRP2 was asked to wear the textured insoles and GRP1 did not wear the textured insoles. Participants were tested pre-intervention, after 4 weeks, and at 8 weeks for both inversion and eversion ankle discrimination. In both inversion and eversion testing positions, interaction was found between the 2 groups and the 3 testing times (pproprioceptive system arising from textured insoles worn for 4 weeks was sufficient to improve the ankle proprioception of ballet dancers, in both inversion and eversion movements.

  13. Language proficiency modulates the recruitment of non-classical language areas in bilinguals.

    Directory of Open Access Journals (Sweden)

    Matthew K Leonard

    Full Text Available Bilingualism provides a unique opportunity for understanding the relative roles of proficiency and order of acquisition in determining how the brain represents language. In a previous study, we combined magnetoencephalography (MEG and magnetic resonance imaging (MRI to examine the spatiotemporal dynamics of word processing in a group of Spanish-English bilinguals who were more proficient in their native language. We found that from the earliest stages of lexical processing, words in the second language evoke greater activity in bilateral posterior visual regions, while activity to the native language is largely confined to classical left hemisphere fronto-temporal areas. In the present study, we sought to examine whether these effects relate to language proficiency or order of language acquisition by testing Spanish-English bilingual subjects who had become dominant in their second language. Additionally, we wanted to determine whether activity in bilateral visual regions was related to the presentation of written words in our previous study, so we presented subjects with both written and auditory words. We found greater activity for the less proficient native language in bilateral posterior visual regions for both the visual and auditory modalities, which started during the earliest word encoding stages and continued through lexico-semantic processing. In classical left fronto-temporal regions, the two languages evoked similar activity. Therefore, it is the lack of proficiency rather than secondary acquisition order that determines the recruitment of non-classical areas for word processing.

  14. The natural course of non-classic Pompe's disease; a review of 225 published cases.

    Science.gov (United States)

    Winkel, Léon P F; Hagemans, Marloes L C; van Doorn, Pieter A; Loonen, M Christa B; Hop, Wim J C; Reuser, Arnold J J; van der Ploeg, Ans T

    2005-08-01

    Pompe's disease is a neuromuscular disorder caused by deficiency of lysosomal acid alpha-glucosidase. Recombinant human alpha- glucosidase is under evaluation as therapeutic drug. In light of this development we studied the natural course of cases not fitting the definition of classic infantile Pompe's disease. Our review of 109 reports including 225 cases shows a continuous spectrum of phenotypes. The onset of symptoms ranged from 0 to 71 years. Based on the available literature, no criteria to delineate clinical sub-types could be established.A common denominator of these cases is that first symptoms were related to or caused by muscle weakness. In general, patients with a later onset of symptoms seemed to have a better prognosis. Respiratory failure was the most frequent cause of death. CK, LDH, ASAT, ALAT and muscle glycogen levels were frequently but not always elevated. In most cases a muscle biopsy revealed lysosomal pathology, but normal muscle morphology does not exclude Pompe's disease. In 10% of the cases in which the enzyme assay on leukocytes was used, a normal alpha-glucosidase activity was reported. Data on skeletal muscle strength and function, pulmonary function, disability, handicap and quality of life were insufficiently reported in the literature. Studies of non-classic Pompe's disease should focus on these aspects, before enzyme replacement therapy becomes generally available.

  15. Language proficiency modulates the recruitment of non-classical language areas in bilinguals.

    Science.gov (United States)

    Leonard, Matthew K; Torres, Christina; Travis, Katherine E; Brown, Timothy T; Hagler, Donald J; Dale, Anders M; Elman, Jeffrey L; Halgren, Eric

    2011-03-24

    Bilingualism provides a unique opportunity for understanding the relative roles of proficiency and order of acquisition in determining how the brain represents language. In a previous study, we combined magnetoencephalography (MEG) and magnetic resonance imaging (MRI) to examine the spatiotemporal dynamics of word processing in a group of Spanish-English bilinguals who were more proficient in their native language. We found that from the earliest stages of lexical processing, words in the second language evoke greater activity in bilateral posterior visual regions, while activity to the native language is largely confined to classical left hemisphere fronto-temporal areas. In the present study, we sought to examine whether these effects relate to language proficiency or order of language acquisition by testing Spanish-English bilingual subjects who had become dominant in their second language. Additionally, we wanted to determine whether activity in bilateral visual regions was related to the presentation of written words in our previous study, so we presented subjects with both written and auditory words. We found greater activity for the less proficient native language in bilateral posterior visual regions for both the visual and auditory modalities, which started during the earliest word encoding stages and continued through lexico-semantic processing. In classical left fronto-temporal regions, the two languages evoked similar activity. Therefore, it is the lack of proficiency rather than secondary acquisition order that determines the recruitment of non-classical areas for word processing.

  16. NATO Advanced Research Workshop on Squeezed and Non-classical Light

    CERN Document Server

    Pike, E; Squeezed and Non-classical Light

    1988-01-01

    The recent generation in the laboratory of phase squeezed and intensity squeezed light beams has brought to fruition the theoretical predictions of such non-classical phenomena which have been made and developed in recent years by a number of workers in the field of quantum optics. A vigorous development is now underway of both theory and experiment and the first measurements have been coi:Jfirmed and extended already in some half dozen laboratories. Although the fields of application of these novellight sources are as yet somewhat hazy in our minds and some inspired thinking is required along these lines, the pace and excitement of the research is very clear. It is to he hoped that the new possibilities of: making measurements below the quantum shot noise lirnit which is made possible by these squeezed states of light willlead to further fundamental advances in the near future. In this NATO ARW a number of the leaders in the field met in the extremely pleasant surroundings of Cortina d'Ampezzo and th...

  17. Observations on non-classical behavior of solid 4He with compound torsional oscillator

    Science.gov (United States)

    Keiderling, M. C.; Aoki, Y.; Kojima, H.

    2009-02-01

    The response of oscillating hcp solid 4He samples was studied with a unique compound torsional oscillator a dummy mass and a sample (cylindrical or annular) container connected by two torsion rods. Identical solid sample could be probed within the same apparatus at two different frequencies (~ 0.5 and 1.2 kHz) separately or simultaneously. The apparent onset of the non-classical rotational inertia (NCRI) occurred at a higher temperature in the higher frequency mode. The peak in dissipation of the higher mode also occurred at higher temperature. Surprisingly, the mechanical dissipation was significantly greater in the lower mode. When the lower mode was driven at high levels to induce "critical state" in the sample and the higher mode was simultaneously driven at a low level for probing, the critical state seen in the lower mode did not entirely appear. Conversely, if a critical state was induced by the higher mode, it also did not appear in the lower mode. These preliminary results are contrary to the simple expectation from identifying the critical state as indication of suppressed superfluid density.

  18. Identification and estimation of nonlinear models using two samples with nonclassical measurement errors

    KAUST Repository

    Carroll, Raymond J.

    2010-05-01

    This paper considers identification and estimation of a general nonlinear Errors-in-Variables (EIV) model using two samples. Both samples consist of a dependent variable, some error-free covariates, and an error-prone covariate, for which the measurement error has unknown distribution and could be arbitrarily correlated with the latent true values; and neither sample contains an accurate measurement of the corresponding true variable. We assume that the regression model of interest - the conditional distribution of the dependent variable given the latent true covariate and the error-free covariates - is the same in both samples, but the distributions of the latent true covariates vary with observed error-free discrete covariates. We first show that the general latent nonlinear model is nonparametrically identified using the two samples when both could have nonclassical errors, without either instrumental variables or independence between the two samples. When the two samples are independent and the nonlinear regression model is parameterized, we propose sieve Quasi Maximum Likelihood Estimation (Q-MLE) for the parameter of interest, and establish its root-n consistency and asymptotic normality under possible misspecification, and its semiparametric efficiency under correct specification, with easily estimated standard errors. A Monte Carlo simulation and a data application are presented to show the power of the approach.

  19. JAK-STAT pathway in carcinogenesis: Is it relevant to cholangiocarcinoma progression?

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The features of JAK-STAT signaling in liver cells are discussed in the current review. The role of this signaling cascade in carcinogenesis is accentuated. The possible involvement of this pathway and alteration of its elements are compared for normal cholangiocytes,cholangiocarcinoma predisposition and development.Prolactin and interleukin-6 are described in detail as the best studied examples. In addition, the non-classical nuclear translocation of cytokine receptors is discussed in terms of its possible implication to cholangiocarcinoma development.

  20. Non-Classical Stress Concentration Behavior in a Radically Stretched Hyperelastic Sheet Containing a Circular Hole

    Science.gov (United States)

    Ko, William L.; Lung, Shun-Fat

    2017-01-01

    Non-classical stress concentration behavior in a stretched circular hyperelastic sheet (outer radius b = 10 in., thickness t = 0.0625 in.) containing a central hole (radius a = 0.5 in.) was analyzed. The hyperelastic sheet was subjected to different levels of remote radial stretchings. Nastran large-strain large-deformation analysis and the Blatz-Ko large deformation theory were used to calculate the equal-biaxial stress concentration factors K. The results show that the values of K calculated from the Blatz-Ko theory and Nastran are extremely close. Unlike the classical linear elasticity theory, which gives the constant K = 2 for the equal-biaxial stress field, the hyperelastic K values were found to increase with increased stretching and can exceed the value K = 6 at a remote radial extension ratio of 2.35. The present K-values compare fairly well with the K-values obtained by previous works. The effect of the hole-size on K-values was investigated. The values of K start to decrease from a hole radius a = 0.125 in. down to K = 1 (no stress concentration) as a shrinks to a = 0 in. (no hole). Also, the newly introduced stretch and strain magnification factors {K(sub ?),K(sub e) } are also material- and deformation-dependent, and can increase from linear levels of {1.0, 4.0} and reaching {3.07, 4.61}, respectively at a remote radial extension ratio of 2.35.

  1. Studying thin film damping in a micro-beam resonator based on non-classical theories

    Science.gov (United States)

    Ghanbari, Mina; Hossainpour, Siamak; Rezazadeh, Ghader

    2016-06-01

    In this paper, a mathematical model is presented for studying thin film damping of the surrounding fluid in an in-plane oscillating micro-beam resonator. The proposed model for this study is made up of a clamped-clamped micro-beam bound between two fixed layers. The micro-gap between the micro-beam and fixed layers is filled with air. As classical theories are not properly capable of predicting the size dependence behaviors of the micro-beam, and also behavior of micro-scale fluid media, hence in the presented model, equation of motion governing longitudinal displacement of the micro-beam has been extracted based on non-local elasticity theory. Furthermore, the fluid field has been modeled based on micro-polar theory. These coupled equations have been simplified using Newton-Laplace and continuity equations. After transforming to non-dimensional form and linearizing, the equations have been discretized and solved simultaneously using a Galerkin-based reduced order model. Considering slip boundary conditions and applying a complex frequency approach, the equivalent damping ratio and quality factor of the micro-beam resonator have been obtained. The obtained values for the quality factor have been compared to those based on classical theories. We have shown that applying non-classical theories underestimate the values of the quality factor obtained based on classical theories. The effects of geometrical parameters of the micro-beam and micro-scale fluid field on the quality factor of the resonator have also been investigated.

  2. Recommendations for treatment of nonclassic congenital adrenal hyperplasia (NCCAH): an update.

    Science.gov (United States)

    Trapp, Christine M; Oberfield, Sharon E

    2012-03-10

    Congenital adrenal hyperplasia (CAH) is a family of autosomal recessive disorders. 21-Hydroxylase deficiency, in which there are mutations in CYP21A2 (the gene encoding the adrenal 21-hydroxylase enzyme), is the most common form (90%) of CAH. In classic CAH there is impaired cortisol production with diagnostic increased levels of 17-OH progesterone. Excess androgen production results in virilization and in the newborn female may cause development of ambiguous external genitalia. Three-fourths of patients with classic CAH also have aldosterone insufficiency, which can result in salt-wasting; in infancy this manifests as shock, hyponatremia and hyperkalemia. CAH has a reported incidence of 1:10,000-1:20,000 births although there is an increased prevalence in certain ethnic groups. Nonclassic CAH (NCCAH) is a less severe form of the disorder, in which there is 20-50% of 21-hydroxylase enzyme activity (vs. 0-5% in classic CAH) and no salt wasting. The degree of symptoms related to androgen excess is variable and may be progressive with age, although some individuals are asymptomatic. NCCAH has an incidence of 1:1000-1:2000 births (0.1-0.2% prevalence) in the White population; an even higher prevalence is noted in certain ethnic groups such as Ashkenazi Jews (1-2%). As many as two-thirds of persons with NCCAH are compound heterozygotes and carry a severe and mild mutation on different alleles. This paper discusses the genetics of NCCAH, along with its variable phenotypic expression, and reviews the clinical course in untreated patients, which includes rapid early childhood growth, advanced skeletal age, premature adrenarche, acne, impaired reproductive function in both sexes and hirsutism as well as menstrual disorders in females. Finally, it addresses treatment with glucocorticoids vs. non treatment and other therapies, particularly with respect to long term issues such as adult metabolic disease including insulin resistance, cardiovascular disease, metabolic syndrome

  3. Studying thin film damping in a micro-beam resonator based on non-classical theories

    Institute of Scientific and Technical Information of China (English)

    Mina Ghanbari; Siamak Hossainpour; Ghader Rezazadeh

    2016-01-01

    In this paper, a mathematical model is presented for studying thin film damping of the surrounding fluid in an in-plane oscillating micro-beam resonator. The proposed model for this study is made up of a clamped-clamped micro-beam bound between two fixed layers. The micro-gap between the micro-beam and fixed layers is filled with air. As classical theories are not properly capable of pre-dicting the size dependence behaviors of the micro-beam, and also behavior of micro-scale fluid media, hence in the presented model, equation of motion governing longitudinal displacement of the micro-beam has been extracted based on non-local elasticity theory. Furthermore, the fluid field has been modeled based on micro-polar theory. These coupled equations have been simplified using Newton-Laplace and continuity equations. After transforming to non-dimensional form and linearizing, the equations have been discretized and solved simultaneously using a Galerkin-based reduced order model. Considering slip boundary conditions and applying a complex frequency approach, the equivalent damping ratio and quality factor of the micro-beam resonator have been obtained. The obtained values for the quality factor have been compared to those based on classical theories. We have shown that applying non-classical theories underestimate the values of the quality factor obtained based on classical theo-ries. The effects of geometrical parameters of the micro-beam and micro-scale fluid field on the quality factor of the res-onator have also been investigated.

  4. Does a nonclassical signaling mechanism underlie an increase of estradiol-mediated gonadotropin-releasing hormone receptor binding in ovine pituitary cells?

    Science.gov (United States)

    Davis, Tracy L; Whitesell, Jennifer D; Cantlon, Jeremy D; Clay, Colin M; Nett, Terry M

    2011-10-01

    Estradiol-17beta (E2) is the major regulator of GnRH receptor (GnRHR) gene expression and number during the periovulatory period; however, the mechanisms underlying E2 regulation of the GNRHR gene remain undefined. Herein, we find that E2 conjugated to BSA (E2-BSA) mimics the stimulatory effect of E2 on GnRH binding in primary cultures of ovine pituitary cells. The time course for maximal GnRH analog binding was similar for both E2 and E2-BSA. The ability of E2 and E2-BSA to increase GnRH analog binding was blocked by the estrogen receptor (ER) antagonist ICI 182,780. Also, increased GnRH analog binding in response to E2 and the selective ESR1 agonist propylpyrazole triol was blocked by expression of a dominant-negative form of ESR1 (L540Q). Thus, membrane-associated ESR1 is the likely candidate for mediating E2 activation of the GNRHR gene. As cAMP response element binding protein (CREB) is an established target for E2 activation in gonadotrophs, we next explored a potential role for this protein as an intracellular mediator of the E2 signal. Consistent with this possibility, adenoviral-mediated expression of a dominant-negative form of CREB (A-CREB) completely abolished the ability of E2 to increase GnRH analog binding in primary cultures of ovine pituitary cells. Finally, the presence of membrane-associated E2 binding sites on ovine pituitary cells was demonstrated using a fluorescein isothiocyanate conjugate of E2-BSA. We suggest that E2 regulation of GnRHR number during the preovulatory period reflects a membrane site of action and may proceed through a nonclassical signaling mechanism, specifically a CREB-dependent pathway.

  5. Nucleation pathway in coherent precipitation

    Science.gov (United States)

    Philippe, T.; Blavette, D.

    2011-12-01

    The non-classical nucleation pathway of coherent precipitates has been computed through minimisation of the nucleation barrier in the composition (c)-size (R) space to predict the evolution of nucleus composition. The generalized Gibbs model, developed by Schmelzer et al. [J. Chem. Phys. 112 (2000) p.3820; J. Colloid Interface Sci. 272 (2004) p.109], has been extended to include misfit elastic energy. The composition of critical embryos c* was found to be independent of the interfacial constant. The composition of critical nuclei (c*) decreased with supersaturation. The elastic energy increased both c* and the nucleation barrier, as well as R*. The evolution of nucleus composition (c) as a function of size (R) along the minimum energy pathway was computed. Nucleation only starts when a size threshold is exceeded. Then, rapid enrichment to the expected composition (c β) precedes a constant composition regime. However, for small supersaturations, the change in cluster composition can occur sharply for a very small radius and then the composition slowly increased with a significant change in size. Coherency misfit energy was found to slow down the evolution of nuclei composition with R. The model was compared to experimental results.

  6. A nonclassical Radau collocation method for solving the Lane-Emden equations of the polytropic index 4.75 ≤ α < 5

    Science.gov (United States)

    Tirani, M. D.; Maleki, M.; Kajani, M. T.

    2014-11-01

    A numerical method for solving the Lane-Emden equations of the polytropic index α when 4.75 ≤ α ≤ 5 is introduced. The method is based upon nonclassical Gauss-Radau collocation points and Freud type weights. Nonclassical orthogonal polynomials, nonclassical Radau points and weighted interpolation are introduced and are utilized in the interval [0,1]. A smooth, strictly monotonic transformation is used to map the infinite domain x ∈ [0,∞) onto a half-open interval t ∈ [0,1). The resulting problem on the finite interval is then transcribed to a system of nonlinear algebraic equations using collocation. The method is easy to implement and yields very accurate results.

  7. Generation of two types of nonclassical optical states using an optical parametric oscillator with a PPKTP crystal

    Science.gov (United States)

    Huo, Meiru; Qin, Jiliang; Yan, Zhihui; Jia, Xiaojun; Peng, Kunchi

    2016-11-01

    As important members of nonclassical states of light, squeezed states and entangled states are basic resources for realizing quantum measurements and constructing quantum information networks. We experimentally demonstrate that the two types of nonclassical optical states can be generated from an optical parametric oscillator (OPO) involving a periodically poled KTiOPO4 crystal with a domain-inversion period of 51.7 μm, by changing the polarization of the pump laser. When a vertically polarized 671 nm laser is used to pump the OPO, the intra-cavity frequency-down-conversion with type-0 quasi-phase matching is realized and the output optical beam is a quadrature amplitude squeezed state of light at the wavelength of 1342 nm with the fluctuation of quadrature component of 3.17 dB below the quantum noise limit (QNL). If the pump laser is horizontally polarized, the condition of the type-II quasi-phase matching is satisfied and the output optical beam becomes Einstein-Podolsky-Rosen entangled state of light with correlation variances of both quadrature amplitude-sum and quadrature phase-difference of 2.2 dB below the corresponding QNL.

  8. Cognitive aspects of a temporality concept in the comparative analysis of post-nonclassical scientificity and myth

    Directory of Open Access Journals (Sweden)

    Tychkin Pavel

    2016-01-01

    Full Text Available The paper considers ‘time’, a fundamental category of human existence, in the context of cognitive processes research in modern culture. Main methodological approaches to determining temporality in myth have been outlined. The authors validate a thesis that methods of understanding time in science and myth at the current development stage of research of the specified worldview forms as cognitive practices correlate. Main features of a ‘time’ concept and its function in mythological thinking, such as unity, interpenetrability, verticality, have been formulated. Myth creates senses, forms a steady ontological picture of the world, makes a human an active source in “constructing the reality”. In this connection, myth mostly plays the role of one of the algorithms of cognitive activity in the context of modern cognitive science. A “temporality” concept realized in myth forms conditions to use it as one of ontological foundations in the modern research of cognitive processes. Main types of temporality in classical and nonclassical science have been described. The specificity of time concept transformation in non-classical science and actualization of relativity and probability of processes and their complementary nature have been revealed. D.Chou’s bootstrap theory of particles has been studied. There has been shown that temporary processes of the micro-world are discrete, diverse and do not exist within the framework of universal integrity which to a great extent correlates with the modern scientific worldview and principles of cognitive practices.

  9. An efficient nonclassical quadrature for the calculation of nonresonant nuclear fusion reaction rate coefficients from cross section data

    Science.gov (United States)

    Shizgal, Bernie D.

    2016-08-01

    Nonclassical quadratures based on a new set of half-range polynomials, Tn(x) , orthogonal with respect to w(x) =e - x - b /√{ x } for x ∈ [ 0 , ∞) are employed in the efficient calculation of the nuclear fusion reaction rate coefficients from cross section data. The parameter b = B /√{kB T } in the weight function is temperature dependent and B is the Gamow factor. The polynomials Tn(x) satisfy a three term recurrence relation defined by two sets of recurrence coefficients, αn and βn. These recurrence coefficients define in turn the tridiagonal Jacobi matrix whose eigenvalues are the quadrature points and the weights are calculated from the first components of the eigenfunctions. For nonresonant nuclear reactions for which the astrophysical function can be expressed as a lower order polynomial in the relative energy, the convergence of the thermal average of the reactive cross section with this nonclassical quadrature is extremely rapid requiring in many cases 2-4 quadrature points. The results are compared with other libraries of nuclear reaction rate coefficient data reported in the literature.

  10. hBolA, novel non-classical secreted proteins, belonging to different BolA family with functional divergence.

    Science.gov (United States)

    Zhou, Yu-Bo; Cao, Jia-Bing; Wan, Bing-Bing; Wang, Xin-Rong; Ding, Guo-Hui; Zhu, Hong; Yang, Hong-Meng; Wang, Ke-Sheng; Zhang, Xin; Han, Ze-Guang

    2008-10-01

    This study reported that all three human BolA proteins (hBolA1, hBolA2, and hBolA3) are novel non-classical secreted proteins identified with bioinformatics and molecular biology experiments. The three BolA fusion proteins with c-Myc tag could be secreted into the culture medium of the transfected Cos-7 cells, although they could not be colocalized with Golgi apparatus. And the secretion of three BolA proteins could not be inhibited after BFA treatment. Furthermore, the secretion was not dependent on its predicted signal peptide. All the experiment results suggested that the secretion was a non-classical export. Phylogenetic analysis showed that the human BolAs belong to three different groups with functional divergence of BolA subfamily, where the different helix-turn-helix motif among hBolA1, hBolA2, and hBolA3 could be responsible for their functional divergence. Our data provided a basis for functional studies of BolA protein family.

  11. Electrical stimulation of non-classical photon emission from diamond color centers by means of sub-superficial graphitic electrodes.

    Science.gov (United States)

    Forneris, Jacopo; Traina, Paolo; Monticone, Daniele Gatto; Amato, Giampiero; Boarino, Luca; Brida, Giorgio; Degiovanni, Ivo P; Enrico, Emanuele; Moreva, Ekaterina; Grilj, Veljko; Skukan, Natko; Jakšić, Milko; Genovese, Marco; Olivero, Paolo

    2015-10-29

    Focused MeV ion beams with micrometric resolution are suitable tools for the direct writing of conductive graphitic channels buried in an insulating diamond bulk, as already demonstrated for different device applications. In this work we apply this fabrication method to the electrical excitation of color centers in diamond, demonstrating the potential of electrical stimulation in diamond-based single-photon sources. Differently from optically-stimulated light emission from color centers in diamond, electroluminescence (EL) requires a high current flowing in the diamond subgap states between the electrodes. With this purpose, buried graphitic electrode pairs, 10 μm spaced, were fabricated in the bulk of a single-crystal diamond sample using a 6 MeV C microbeam. The electrical characterization of the structure showed a significant current injection above an effective voltage threshold of 150 V, which enabled the stimulation of a stable EL emission. The EL imaging allowed to identify the electroluminescent regions and the residual vacancy distribution associated with the fabrication technique. Measurements evidenced isolated electroluminescent spots where non-classical light emission in the 560-700 nm spectral range was observed. The spectral and auto-correlation features of the EL emission were investigated to qualify the non-classical properties of the color centers.

  12. Measures of nonclassicality for a two-level atom interacting with power-law potential field under decoherence effect

    Science.gov (United States)

    Abdel-Khalek, S.; Berrada, K.; Alkhateeb, Sadah A.

    2016-09-01

    In this paper, we propose a useful quantum system to perform different tasks of quantum information and computational technologies. We explore the required optimal conditions for this system that are feasible with real experimental realization. We present an active way to control the variation of some measures of nonclassicality considering the time-dependent coupling and photon transition effects under a model that closely describes a realistic experimental scenario. We investigate qualitatively the quantum measures for a two-level atom system interacting with a quantum field initially defined in a coherent state in the framework of power-law potentials (PLPCSs). We study the nonlocal correlation in the whole system state using the negativity as a measure of entanglement in terms of the exponent parameter, number of photon transition, and phase damping effect. The influences of the different physical parameters on the statistical properties and purity of the field are also demonstrated during the time evolution. The results indicate that the preservation and enhancement of entanglement greatly benefit from the combination of the choice of the physical parameters. Finally, we explore an interesting relationship between the different quantum measures of non-classicality during the time evolution in the absence and presence of time-dependent coupling effect.

  13. Mechanisms involved in vitamin D mediated intestinal calcium absorption and in non-classical actions of vitamin D.

    Science.gov (United States)

    Christakos, Sylvia; Dhawan, Puneet; Ajibade, Dare; Benn, Bryan S; Feng, Jingjing; Joshi, Sneha S

    2010-07-01

    Recent studies in our laboratory using calbindin-D9k null mutant mice as well as mice lacking the 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) inducible epithelial calcium channel TRPV6 provide evidence for calbindin-D9k and TRPV6 independent regulation of active intestinal calcium absorption. These findings suggest that in the knock out (KO) mice there is compensation by another calcium channel or protein and that other novel factors are involved in 1,25(OH)2D3 mediated active intestinal calcium absorption. In addition, 1,25(OH)2D3 mediated paracellular transport of calcium may have contributed to the normalization of serum calcium in the null mutant mice. 1,25(OH)2D3 downregulates cadherin-17 and upregulates claudin-2 and claudin-12 in the intestine, suggesting that 1,25(OH)2D3, by regulating these epithelial cell junction proteins, can route calcium through the paracellular path. With regard to non-classical actions, 1,25(OH)2D3 has been reported to inhibit the proliferation of a number of malignant cells and to regulate adaptive as well as innate immunity. This article will review new developments related to the function and regulation of vitamin D target proteins in classical and non-classical vitamin D target tissues that have provided novel insight into mechanisms of vitamin D action.

  14. Hydrogenation of Liquid Styrene by Alumina Supported Nickel Catalysts: Comparison between Classical and Non-Classical Methods

    Science.gov (United States)

    Tan, Y. C.; Abu Bakar, N. H. H.; Tan, W. L.; Abu Bakar, M.

    2016-06-01

    Almina supported Ni catalysts (Ni/Al2O3) with different Ni weight percentages (wt%) were prepared via classical and non-classical methods. All samples were prepared via impregnation technique. The samples prepared via non-classical methods were reduced using KBH4 as the reducing agent. The catalysts were tested for the hydrogenation of styrene in liquid phase. Optimum activation conditions for the hydrogenation reaction were found to be 633 K for 2 hours. Comparison of the catalytic reactivity for all catalysts at these activation conditions showed that catalysts prepared via classical methods exhibited better activity. Furthermore the 7.6wt% Ni-Al2O3/C showed enhanced activity when compared to the 5.9wt% and 13.8wt% Ni-Al2O3/C catalyst. This phenomenon is mainly attributed to the type of Ni active sites available on the catalyst. The surface properties of the catalysts investigated via H2- temperature programmed reduction (H2-TPR), H2-chemisorption and H2-temperature programmed desorption (H2-TPD) confirm this.

  15. Recent Insights Into the Prenucleation Cluster Pathway

    Science.gov (United States)

    Gebauer, D.; Kellermeier, M.; Berg, J. K.

    2012-12-01

    Stable calcium carbonate pre-nucleation clusters (PNCs) form in aqueous solution prior to nucleation of CaCO3 (1). Computer simulations suggest that the thermodynamic stability of PNCs is based upon strong hydration in combination with a distinct entropic contribution (2). In this way, PNCs can compete enthalpically with ion pairs and entropically with amorpous calcium carbonate (ACC). The clue is a high degree of structural disorder in highly dynamic, liquid- and chain-like polymeric structures of calcium carbonate ion pairs (2). Nucleation of solid calcium carbonate from these polymeric species proceeds via PNC aggregation rather than via ion-by-ion additions to un-/metastable nuclei (3). Owing to these basic characteristics, the pre-nucleation cluster pathway has been referred to as "non-classical nucleation" (4). Non-classical nucleation leads to distinct short-range structural features in ACC, and depending on pH they relate to the crystalline long-range order of calcite or vaterite (5). This suggests that calcium carbonate exhibits polyamorphism, and that distinct polyamorphs may play a central role during polymorph selection. In this contribution, we outline the scenario described above, and focus on recent insights into the pre-nucleation cluster pathway. 1. D. Gebauer, A. Völkel & H. Cölfen, Science 322, 1819-1822 (2008). 2. R. Demichelis, P. Raiteri, J.D. Gale, D. Quigley, D. Gebauer, Nat. Commun. 2, 590 (2011). 3. M. Kellermeier et al., Adv. Funct. Mater., DOI: 10.1002/adfm.201200953 (2012). 4. D. Gebauer, H. Cölfen, Nano Today 6, 564-584 (2011). 5. D. Gebauer et al., Angew. Chem. Int. Ed. 49, 8889-8891 (2010).

  16. 负相伴随机变量的非经典重对数律%A NONCLASSICAL LAW OF ITERATED LOGARITHM FOR NEGATIVELY ASSOCIATED RANDOM VARIABLES

    Institute of Scientific and Technical Information of China (English)

    蒋烨

    2003-01-01

    A nonclassical law of iterated logarithm that holds for a stationary negativelyassociated sequence of random variables with finite variance is proved in this paperThe proof isbased on a Rosenthal type maximal inequality and the subsequence metlodThis result extendsthe work of Klesov,Rosalsky (2001) and Shao,Su (1999).

  17. A quantum-information theoretic analysis of three-flavor neutrino oscillations. Quantum entanglement, nonlocal and nonclassical features of neutrinos

    Science.gov (United States)

    Banerjee, Subhashish; Alok, Ashutosh Kumar; Srikanth, R.; Hiesmayr, Beatrix C.

    2015-10-01

    Correlations exhibited by neutrino oscillations are studied via quantum-information theoretic quantities. We show that the strongest type of entanglement, genuine multipartite entanglement, is persistent in the flavor changing states. We prove the existence of Bell-type nonlocal features, in both its absolute and genuine avatars. Finally, we show that a measure of nonclassicality, dissension, which is a generalization of quantum discord to the tripartite case, is nonzero for almost the entire range of time in the evolution of an initial electron-neutrino. Via these quantum-information theoretic quantities, capturing different aspects of quantum correlations, we elucidate the differences between the flavor types, shedding light on the quantum-information theoretic aspects of the weak force.

  18. Confirmation of non-classical laws in nonequilibrium gases and application of conservation laws to verification of DSMC

    Science.gov (United States)

    Myong, R. S.; Park, J. H.

    2012-11-01

    The constitutive laws, which describe the material's inherent properties, play a special role in the study of materials such as gases. In this study, the validity of non-classical constitutive laws in rarefied and micro gases is first considered. In particular, non-Navier and non-Fourier laws in algebraic forms identified in the velocity shear gas flows are investigated using DSMC. In addition, a new method based on the conservation laws is applied to the Couette flow and shock structure problems for the verification study of the DSMC. It is shown that, in flow problems involving with the wall boundary condition, the pressure among various properties is the most critical quantity in the verification and validation study of rarefied and micro gases. Such observation may imply the need of further theoretical and experimental investigation on the whole pressure and temperature flowfields beyond a reduced quantity such as the mass flow rate in the Poiseuille gas flows.

  19. Entanglement and nonclassicality in four-mode Gaussian states generated via parametric down-conversion and frequency up-conversion

    Science.gov (United States)

    Arkhipov, Ievgen I.; Peřina, Jan, Jr.; Haderka, Ondřej; Allevi, Alessia; Bondani, Maria

    2016-09-01

    Multipartite entanglement and nonclassicality of four-mode Gaussian states generated in two simultaneous nonlinear processes involving parametric down-conversion and frequency up-conversion are analyzed assuming the vacuum as the initial state. Suitable conditions for the generation of highly entangled states are found. Transfer of the entanglement from the down-converted modes into the up-converted ones is also suggested. The analysis of the whole set of states reveals that sub-shot-noise intensity correlations between the equally-populated down-converted modes, as well as the equally-populated up-converted modes, uniquely identify entangled states. They represent a powerful entanglement identifier also in other cases with arbitrarily populated modes.

  20. Nonclassicality in an atom-molecule Bose-Einstein condensate: Higher-order squeezing, antibunching and entanglement

    Science.gov (United States)

    Giri, Sandip Kumar; Thapliyal, Kishore; Sen, Biswajit; Pathak, Anirban

    2017-01-01

    The transient quantum statistical properties of the atoms and molecules in an atom-molecule BEC system are investigated by obtaining a third-order perturbative solution of the Heisenberg's equations of motion corresponding to the Hamiltonian of the system, where two atoms can collide to form a molecule. Time dependent quantities, like two boson correlation, entanglement, squeezing, antibunching, etc., are computed, and their properties are compared. It is established that the atom-molecule BEC system is highly nonclassical as lower-order and higher-order squeezing and antibunching in pure (atomic and molecular) modes, squeezing and antibunching in compound mode, and lower-order and higher-order entanglement in compound mode can be observed in the atom-molecule BEC system. Exact numerical results are also reported and the analytic results obtained using the perturbative technique are shown to agree with the exact numerical results.

  1. Nonclassicality and Entanglement of Photon-Subtracted Two-Mode Squeezed Coherent States Studied via Entangled-States Representation

    Science.gov (United States)

    Wang, Zhen; Li, Heng-Mei; Yuan, Hong-Chun

    2016-10-01

    We theoretically introduce a kind of non-Gaussian entangled states, i.e., photon-subtracted two-mode squeezed coherent states (PSTMSCS), by successively subtracting photons from each mode of the two-mode squeezed coherent states. The normalization factor which is related to bivariate Hermite polynomials is obtained by virtue of the two-mode squeezing operator in entangled-states representation. The sub-Poissonian photon statistics, antibunching effects, and partial negative Wigner function, respectively, are observed numerically, which fully reflect the nonclassicality of the resultant states. Finally, employing the SV criteria and the EPR correlation, respectively, the entangled property of PSTMSCS is analyzed. It is shown that the photon subtraction operation can effectively enhance the inseparability between the two modes.

  2. A quantum-information theoretic analysis of three-flavor neutrino oscillations. Quantum entanglement, nonlocal and nonclassical features of neutrinos

    Energy Technology Data Exchange (ETDEWEB)

    Banerjee, Subhashish; Alok, Ashutosh Kumar [Indian Institute of Technology Jodhpur, Jodhpur (India); Srikanth, R. [Poornaprajna Institute of Scientific Research, Banglore (India); Hiesmayr, Beatrix C. [University of Vienna, Vienna (Austria)

    2015-10-15

    Correlations exhibited by neutrino oscillations are studied via quantum-information theoretic quantities. We show that the strongest type of entanglement, genuine multipartite entanglement, is persistent in the flavor changing states. We prove the existence of Bell-type nonlocal features, in both its absolute and genuine avatars. Finally, we show that a measure of nonclassicality, dissension, which is a generalization of quantum discord to the tripartite case, is nonzero for almost the entire range of time in the evolution of an initial electron-neutrino. Via these quantum-information theoretic quantities, capturing different aspects of quantum correlations, we elucidate the differences between the flavor types, shedding light on the quantum-information theoretic aspects of the weak force. (orig.)

  3. Entanglement and nonclassicality in four-mode Gaussian states generated via parametric down-conversion and frequency up-conversion

    Science.gov (United States)

    Arkhipov, Ievgen I.; Peřina Jr., Jan; Haderka, Ondřej; Allevi, Alessia; Bondani, Maria

    2016-01-01

    Multipartite entanglement and nonclassicality of four-mode Gaussian states generated in two simultaneous nonlinear processes involving parametric down-conversion and frequency up-conversion are analyzed assuming the vacuum as the initial state. Suitable conditions for the generation of highly entangled states are found. Transfer of the entanglement from the down-converted modes into the up-converted ones is also suggested. The analysis of the whole set of states reveals that sub-shot-noise intensity correlations between the equally-populated down-converted modes, as well as the equally-populated up-converted modes, uniquely identify entangled states. They represent a powerful entanglement identifier also in other cases with arbitrarily populated modes. PMID:27658508

  4. Barut-Girardello and Gilmore-Perelomov coherent states for pseudoharmonic oscillators and their nonclassical properties:Factorization method

    Institute of Scientific and Technical Information of China (English)

    M K Tavassoly; H R Jalali

    2013-01-01

    In this paper we try to introduce the ladder operators associated with the pseudoharmonic oscillator,after solving the corresponding Schr(o)dinger equation by using the factorization method.The obtained generalized raising and lowering operators naturally lead us to the Dirac representation space of the system which is much easier to work with,in comparison to the functional Hilbert space.The SU (1,1) dynamical symmetry group associated with the considered system is exactly established through investigating the fact that the deduced operators satisfy appropriate commutation relations.This result enables us to construct two important and distinct classes of Barut-Girardello and Gilmore-Perelomov coherent states associated with the system.Finally,their identities as the most important task are exactly resolved and some of their nonclassical properties are illustrated,numerically.

  5. Nonclassical dynamics of the methyl group in 1,1,1-triphenylethane. Evidence from powder 1H NMR spectra

    KAUST Repository

    Osior, Agnieszka

    2017-03-14

    According to the damped quantum rotation (DQR) theory, hindered rotation of methyl groups, evidenced in nuclear magnetic resonance (NMR) line shapes, is a nonclassical process. It comprises a number of quantum-rate processes measured by two different quantum-rate constants. The classical jump model employing only one rate constant is reproduced if these quantum constants happen to be equal. The values of their ratio, or the nonclassicallity coefficient, determined hitherto from NMR spectra of single crystals and solutions range from about 1.20 to 1.30 in the latter case to above 5.0 in the former, with the value of 1 corresponding to the jump model. Presently, first systematic investigations of the DQR effects in wide-line NMR spectra of a powder sample are reported. For 1,1,1-triphenylethane deuterated in the aromatic positions, the relevant line-shape effects were monitored in the range 99–121 K. The values of the nonclassicality coefficient dropping from 2.7 to 1.7 were evaluated in line shape fits to the experimental powder spectra from the range 99–108 K. At these temperatures, the fits with the conventional line-shape model are visibly inferior to the DQR fits. Using a theoretical model reported earlier, a semiquantitative interpretation of the DQR parameters evaluated from the spectra is given. It is shown that the DQR effects as such can be detected in wide-line NMR spectra of powdered samples, which are relatively facile to measure. However, a fully quantitative picture of these effects can only be obtained from the much more demanding experiments on single crystals.

  6. Sequence and mRNA expression of nonclassical SLA class I genes SLA-7 and SLA-8.

    Science.gov (United States)

    Crew, Mark D; Phanavanh, Bounleut; Garcia-Borges, Carmen N

    2004-05-01

    Given the prominent position of pig endothelial cells in pig-to-human xenotransplantation and the role of classical and nonclassical MHC class I proteins in T and NK cell recognition, the expression of pig MHC (SLA) class I genes in a pig aortic endothelial cell line (AOC cells) was examined. Using a primer corresponding to a highly conserved region of exon 4, RT-PCR analysis of SLA class I expression in AOC cells revealed not only expression of the classical SLA class I ( SLA-1, -2, and -3) genes, but also SLA class I transcripts corresponding to SLA nonclassical class I (class Ib) genes SLA-6 and SLA-8. Further analysis of SLA class Ib expression in porcine aortic endothelial cells using SLA class I gene-specific primers confirmed SLA-6 and SLA-8 expression and also demonstrated expression of SLA-7. While SLA-6 has been relatively well characterized, no data regarding bona fide SLA-7 and SLA-8 transcripts have been reported. Therefore, cDNAs containing the complete open reading frames of SLA-6, -7, and -8 were obtained. Compared to an SLA-1 protein sequence, the predicted SLA-7 and -8 protein sequences exhibited most sequence divergence in alpha1, alpha2, and cytoplasmic domains. Expression of SLA-6, -7, and -8 was examined by RT-PCR using RNA prepared from a variety of tissues. SLA-6 transcripts were detected in every tissue examined. Except for brain, SLA-8 transcripts were similarly widespread. SLA-7 exhibited more limited tissue distribution.

  7. Nuclear translocation of glutathione S-transferase {pi} is mediated by a non-classical localization signal

    Energy Technology Data Exchange (ETDEWEB)

    Kawakatsu, Miho [Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523 (Japan); Goto, Shinji, E-mail: sgoto@nagasaki-u.ac.jp [Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523 (Japan); Yoshida, Takako; Urata, Yoshishige; Li, Tao-Sheng [Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523 (Japan)

    2011-08-12

    Highlights: {yields} Nuclear translocation of GST{pi} is abrogated by the deletion of the last 16 amino acid residues in the carboxy-terminal region, indicating that residues 195-208 of GST{pi} are required for nuclear translocation. {yields} The lack of a contiguous stretch of positively charged amino acid residues within the carboxy-terminal region of GST{pi}, suggests that the nuclear translocation of GST{pi} is mediated by a non-classical nuclear localization signal. {yields} An in vitro transport assay shows that the nuclear translocation of GST{pi} is dependent on cytosolic factors and ATP. -- Abstract: Glutathione S-transferase {pi} (GST{pi}), a member of the GST family of multifunctional enzymes, is highly expressed in human placenta and involved in the protection of cellular components against electrophilic compounds or oxidative stress. We have recently found that GST{pi} is expressed in the cytoplasm, mitochondria, and nucleus in some cancer cells, and that the nuclear expression of GST{pi} appears to correlate with resistance to anti-cancer drugs. Although the mitochondrial targeting signal of GST{pi} was previously identified in the amino-terminal region, the mechanism of nuclear translocation remains completely unknown. In this study, we find that the region of GST{pi}195-208 is critical for nuclear translocation, which is mediated by a novel and non-classical nuclear localization signal. In addition, using an in vitro transport assay, we demonstrate that the nuclear translocation of GST{pi} depends on the cytosolic extract and ATP. Although further experiments are needed to understand in depth the precise mechanism of nuclear translocation of GST{pi}, our results may help to establish more efficient anti-cancer therapy, especially with respect to resistance to anti-cancer drugs.

  8. Characterization of novel StAR (steroidogenic acute regulatory protein mutations causing non-classic lipoid adrenal hyperplasia.

    Directory of Open Access Journals (Sweden)

    Christa E Flück

    Full Text Available CONTEXT: Steroidogenic acute regulatory protein (StAR is crucial for transport of cholesterol to mitochondria where biosynthesis of steroids is initiated. Loss of StAR function causes lipoid congenital adrenal hyperplasia (LCAH. OBJECTIVE: StAR gene mutations causing partial loss of function manifest atypical and may be mistaken as familial glucocorticoid deficiency. Only a few mutations have been reported. DESIGN: To report clinical, biochemical, genetic, protein structure and functional data on two novel StAR mutations, and to compare them with published literature. SETTING: Collaboration between the University Children's Hospital Bern, Switzerland, and the CIBERER, Hospital Vall d'Hebron, Autonomous University, Barcelona, Spain. PATIENTS: Two subjects of a non-consanguineous Caucasian family were studied. The 46,XX phenotypic normal female was diagnosed with adrenal insufficiency at the age of 10 months, had normal pubertal development and still has no signs of hypergonodatropic hypogonadism at 32 years of age. Her 46,XY brother was born with normal male external genitalia and was diagnosed with adrenal insufficiency at 14 months. Puberty was normal and no signs of hypergonadotropic hypogonadism are present at 29 years of age. RESULTS: StAR gene analysis revealed two novel compound heterozygote mutations T44HfsX3 and G221S. T44HfsX3 is a loss-of-function StAR mutation. G221S retains partial activity (∼30% and is therefore responsible for a milder, non-classic phenotype. G221S is located in the cholesterol binding pocket and seems to alter binding/release of cholesterol. CONCLUSIONS: StAR mutations located in the cholesterol binding pocket (V187M, R188C, R192C, G221D/S seem to cause non-classic lipoid CAH. Accuracy of genotype-phenotype prediction by in vitro testing may vary with the assays employed.

  9. Origin of the nucleus and Ran-dependent transport to safeguard ribosome biogenesis in a chimeric cell.

    Science.gov (United States)

    Jékely, Gáspár

    2008-07-24

    The origin of the nucleus is a central problem about the origin of eukaryotes. The common ancestry of nuclear pore complexes (NPC) and vesicle coating complexes indicates that the nucleus evolved via the modification of a pre-existing endomembrane system. Such an autogenous scenario is cell biologically feasible, but it is not clear what were the selective or neutral mechanisms that had led to the origin of the nuclear compartment. A key selective force during the autogenous origin of the nucleus could have been the need to segregate ribosome factories from the cytoplasm where ribosomal proteins (RPs) of the protomitochondrium were synthesized. After its uptake by an anuclear cell the protomitochondrium transferred several of its RP genes to the host genome. Alphaproteobacterial RPs and archaebacterial-type host ribosomes were consequently synthesized in the same cytoplasm. This could have led to the formation of chimeric ribosomes. I propose that the nucleus evolved when the host cell compartmentalised its ribosome factories and the tightly linked genome to reduce ribosome chimerism. This was achieved in successive stages by first evolving karyopherin and RanGTP dependent chaperoning of RPs, followed by the evolution of a membrane network to serve as a diffusion barrier, and finally a hydrogel sieve to ensure selective permeability at nuclear pores. Computer simulations show that a gradual segregation of cytoplasm and nucleoplasm via these steps can progressively reduce ribosome chimerism. Ribosome chimerism can provide a direct link between the selective forces for and the mechanisms of evolving nuclear transport and compartmentalisation. The detailed molecular scenario presented here provides a solution to the gradual evolution of nuclear compartmentalization from an anuclear stage. This article was reviewed by Eugene V Koonin, Martijn Huynen, Anthony M. Poole and Patrick Forterre.

  10. Origin of the nucleus and Ran-dependent transport to safeguard ribosome biogenesis in a chimeric cell

    Directory of Open Access Journals (Sweden)

    Jékely Gáspár

    2008-07-01

    Full Text Available Abstract Background The origin of the nucleus is a central problem about the origin of eukaryotes. The common ancestry of nuclear pore complexes (NPC and vesicle coating complexes indicates that the nucleus evolved via the modification of a pre-existing endomembrane system. Such an autogenous scenario is cell biologically feasible, but it is not clear what were the selective or neutral mechanisms that had led to the origin of the nuclear compartment. Results A key selective force during the autogenous origin of the nucleus could have been the need to segregate ribosome factories from the cytoplasm where ribosomal proteins (RPs of the protomitochondrium were synthesized. After its uptake by an anuclear cell the protomitochondrium transferred several of its RP genes to the host genome. Alphaproteobacterial RPs and archaebacterial-type host ribosomes were consequently synthesized in the same cytoplasm. This could have led to the formation of chimeric ribosomes. I propose that the nucleus evolved when the host cell compartmentalised its ribosome factories and the tightly linked genome to reduce ribosome chimerism. This was achieved in successive stages by first evolving karyopherin and RanGTP dependent chaperoning of RPs, followed by the evolution of a membrane network to serve as a diffusion barrier, and finally a hydrogel sieve to ensure selective permeability at nuclear pores. Computer simulations show that a gradual segregation of cytoplasm and nucleoplasm via these steps can progressively reduce ribosome chimerism. Conclusion Ribosome chimerism can provide a direct link between the selective forces for and the mechanisms of evolving nuclear transport and compartmentalisation. The detailed molecular scenario presented here provides a solution to the gradual evolution of nuclear compartmentalization from an anuclear stage. Reviewers This article was reviewed by Eugene V Koonin, Martijn Huynen, Anthony M. Poole and Patrick Forterre.

  11. A Density Functional Study on the Hydrolysis Process of Non-classical Transplatin(Ⅱ) with Two Same Planar Heterocycle Amines

    Institute of Scientific and Technical Information of China (English)

    YUAN Qing-Hui; ZHOU Li-Xin

    2007-01-01

    In the present work, the hydrolysis process of non-classical transplatin(Ⅱ) with two same planar heterocycle amines has been studied using hybrid density functional theory (B3LYP) and IEF-PCM solvation models. Optimizations were performed at the B3LYP level using a combined basis set of (LanL2DZ+6-31+G(d,p)) with single-point energy evaluations using the B3LYP/6-31++G(3df,2pd) approach in vacuo and in aqueous solution. For the obtained structures of reactants, intermediates, transition states, and products, both thermodynamic (reaction energies and Gibbs energies) and kinetic (reaction barriers) characteristics were estimated. In comparison with cisplatin, decreased activation energies were obtained. The result implies that the non-classical transplatin with two same planar heterocycle amines increases the equatorial steric effect and lowers reaction barriers, which may assist in designing novel Pt-based anticancer drugs.

  12. Existence and uniqueness for one-phase Stefan problems of non-classical heat equations with temperature boundary condition at a fixed face

    Directory of Open Access Journals (Sweden)

    Adriana C. Briozzo

    2006-02-01

    Full Text Available We prove the existence and uniqueness, local in time, of a solution for a one-phase Stefan problem of a non-classical heat equation for a semi-infinite material with temperature boundary condition at the fixed face. We use the Friedman-Rubinstein integral representation method and the Banach contraction theorem in order to solve an equivalent system of two Volterra integral equations.

  13. 非经典Ekman方程的解和演化条件%The Developing Conditions and Solutions of Non-classical Ekman's Equation

    Institute of Scientific and Technical Information of China (English)

    林振山

    2003-01-01

    An approximate equation of non-classical Ekman's flow and stochastic equations about Ekman's flow are set up in this paper.The developing conditions,solutions and the frequency response of the non-classical Ekman's flow are studied.The results show that the non-classicalEkman's flow will develop when the classical Ekman's flow shear is large enough and the non-classical Ekman's flow will tend to the most probable state (Us,Vs) or to (-fVe,fUe),respectively,in a similar condition or in a general condition.%建立了一个Ekman边界层的随机方程和非经典Ekman方程,研究了非经典Ekman流的频率响应、解和演化条件.有关研究结果表明,当经典Ekman流的切变足够大时,非经典Ekman流将发展起来,而且在相似条件和普适条件下,非经典Ekman流将分别朝最可几态(Us,Vs)或(-fVe,fU2)演化.

  14. Crystallization of a Nonclassical Kazal-type Carcinoscorpius Rotundicauda Serine Protease Inhibitor, CrSPI-1, Complexed with Subtilisin

    Energy Technology Data Exchange (ETDEWEB)

    Tulsidas, S.; Thangamani, S; Ho, B; Sivaraman, J; Ding, J

    2009-01-01

    Serine proteases play a major role in host-pathogen interactions. The innate immune system is known to respond to invading pathogens in a nonspecific manner. The serine protease cascade is an essential component of the innate immune system of the horseshoe crab. The serine protease inhibitor CrSPI isoform 1 (CrSPI-1), a unique nonclassical Kazal-type inhibitor of molecular weight 9.3 kDa, was identified from the hepatopancreas of the horseshoe crab Carcinoscorpius rotundicauda. It potently inhibits subtilisin and constitutes a powerful innate immune defence against invading microbes. Here, the cloning, expression, purification and cocrystallization of CrSPI-1 with subtilisin are reported. The crystals diffracted to 2.6 {angstrom}resolution and belonged to space group P2{sub 1}, with unit-cell parameters a = 73.8, b = 65.0, c = 111.9 {angstrom}, {beta} = 95.4. The Matthews coefficient (VM = 2.64 {angstrom}3 Da-1, corresponding to 53% solvent content) and analysis of the preliminary structure solution indicated the presence of one heterotrimer (1:2 ratio of CrSPI-1:subtilisin) and one free subtilisin molecule in the asymmetric unit.

  15. Investigation of Non-classical Under lap Design on Linearity of a Folded Cascode Operational Transconductance Amplifier (OTA)

    Science.gov (United States)

    Alam, M. S.; Kranti, A.; Armstrong, G. A.

    2011-08-01

    The significance of optimization of gate-source/drain extension region (also known as a non-classical underlap design) in double gate (DG) silicon-on-insulator (SOI) FETs to improve the linearity performance of a low power folded cascode operational transconductance amplifier (OTA) is described. Based on a new figure-of-merit (FoM) involving AV, linearity, unity gain bandwidth fT and dc power consumption PDC, this article presents guideline for optimum design for underlap spacer s and film thickness Tsi to maximize the performance of OTA. It has been shown that FoM exhibited by an underlap DG MOSFET OTA gives significantly higher value (≅9) compared to a conventional single gate bulk MOSFET OTA. This is due to a combination of both higher fT, and higher gain AV for the same linearity at low power consumption of 360 μW. With gate length scaling, FoM continues to improve, primarily due to higher value of fT. A scaled bulk MOSFET OTA exhibits similar but much smaller enhancement in trend for FoM.

  16. Is basal serum 17-OH progesterone a reliable parameter to predict nonclassical congenital adrenal hyperplasia in premature adrenarche?

    Science.gov (United States)

    Gönç, E Nazli; Ozön, Z Alev; Alikaşifoğlu, Ayfer; Engiz, Ozlem; Bulum, Burcu; Kandemir, Nurgün

    2011-01-01

    To determine the critical features for the diagnosis of nonclassical 21 hydroxylase deficiency (NC210HD) without performing adrenocorticotropic hormone (ACTH) test, we studied 186 cases with premature adrenarche. Clinical and laboratory features as well as basal 17-hydroxyprogesterone (17-OHP) were analyzed to determine factors important for differentiating NC21OHD. Overall, 6 patients (3.2%) had ACTH-stimulated 17-OHP > 10 ng/ml. A cutoff level of 2 ng/ml for basal 17-OHP was 66.7% sensitive and 78% specific for NC21OHD; however, a cutoff level of 1.55 ng/ml had higher sensitivity (83%) and specificity (70.6%). A cutoff of 1.55 ng/ml would lead to 31% of cases with premature adrenarche having to undergo ACTH test, and only one case would have been missed. That case had a bone age SDS > 2. Three cases out of five with a basal 17-OHP > 5 ng/ml had stimulated 17-OHP bone SDS > 2 in those with lower basal levels as a guide for carrying out an ACTH test may yield better results in the diagnosis of NC21OHD in the premature adrenarche population. A cutoff of 5 ng/ml for basal 17-OHP should not be used for diagnosis of NC21OHD.

  17. Improved contour detection model with spatial summation properties based on nonclassical receptive field

    Science.gov (United States)

    Lin, Chuan; Xu, Guili; Cao, Yijun; Liang, Chenghua; Li, Ya

    2016-07-01

    The responses of cortical neurons to a stimulus in a classical receptive field (CRF) can be modulated by stimulating the non-CRF (nCRF) of neurons in the primary visual cortex (V1). In the very early stages (at around 40 ms), a neuron in V1 exhibits strong responses to a small set of stimuli. Later, however (after 100 ms), the neurons in V1 become sensitive to the scene's global organization. As per these visual cortical mechanisms, a contour detection model based on the spatial summation properties is proposed. Unlike in previous studies, the responses of the nCRF to the higher visual cortex that results in the inhibition of the neuronal responses in the primary visual cortex by the feedback pathway are considered. In this model, the individual neurons in V1 receive global information from the higher visual cortex to participate in the inhibition process. Computationally, global Gabor energy features are involved, leading to the more coherent physiological characteristics of the nCRF. We conducted an experiment where we compared our model with those proposed by other researchers. Our model explains the role of the mutual inhibition of neurons in V1, together with an approach for object recognition in machine vision.

  18. Dynamic density functional theory for nucleation: Non-classical predictions of mesoscopic nucleation theory

    Science.gov (United States)

    Duran-Olivencia, Miguel A.; Yatsyshin, Peter; Lutsko, James F.; Kalliadasis, Serafim

    2016-11-01

    Classical density functional theory (DFT) for fluids and its dynamic extension (DDFT) provide an appealing mean-field framework for describing equilibrium and dynamics of complex soft matter systems. For a long time, homogeneous nucleation was considered to be outside the limits of applicability of DDFT. However, our recently developed mesoscopic nucleation theory (MeNT) based on fluctuating hydrodynamics, reconciles the inherent randomness of the nucleation process with the deterministic nature of DDFT. It turns out that in the weak-noise limit, the most likely path (MLP) for nucleation to occur is determined by the DDFT equations. We present computations of MLPs for homogeneous and heterogeneous nucleation in colloidal suspensions. For homogeneous nucleation, the MLP obtained is in excellent agreement with the reduced order-parameter description of MeNT, which predicts a multistage nucleation pathway. For heterogeneous nucleation, the presence of impurities in the fluid affects the MLP, but remarkably, the overall qualitative picture of homogeneous nucleation persists. Finally, we highlight the use of DDFT as a simulation tool, which is especially appealing as there are no known applications of MeNT to heterogeneous nucleation. We acknowledge financial support from the European Research Council via Advanced Grant No. 247031 and from EPSRC via Grants No. EP/L020564 and EP/L025159.

  19. Structure and Magnetic Property Control of Copper Hydroxide Acetate by Non-Classical Crystallization.

    Science.gov (United States)

    Song, RuiQi; Krasia-Christoforou, Theodora; Debus, Christian; Cölfen, Helmut

    2017-03-01

    Copper hydroxide acetate (CHA), one layered hydroxide compound with tunable magnetism, attracts great interest because of its potential applications in memory devices. However, ferromagnetism for CHA is only demonstrated by means of GPa pressure. Herein, a new method is reported, involving the combination of different crystallization pathways to control crystallization of amorphous CHA toward the formation of CHA/polymer composites with tunable magnetic properties and even a tunability that can be tested at room temperature. By using poly[(ethylene glycol)6 methyl ether methacrylate]-block-poly[2-(acetoacetoxy) ethyl methacrylate] (PEGMA-b-PAEMA) diblock copolymers as additives in combination with a post-treatment process by ultracentrifugation, it is demonstrated that CHA and PEGMA-b-PAEMA form composites exhibiting different magnetic properties, depending on CHA in-plane nanostructures. Analytical characterization reveals that crystallization of CHA is induced by ultracentrifugation, during which CHA nanostructures can be well controlled by changing the degrees of polymerization of the PEGMA and PAEMA blocks and their block length ratios. These findings not only present the first example of using crystallization from polymer stabilized amorphous precursors toward the generation of magnetic nanomaterials with tunable magnetism but also pave the way for the future design of functional composite materials.

  20. Tuning crystallization pathways through sequence engineering of biomimetic polymers

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Xiang; Zhang, Shuai; Jiao, Fang; Newcomb, Christina J.; Zhang, Yuliang; Prakash, Arushi; Liao, Zhihao; Baer, Marcel D.; Mundy, Christopher J.; Pfaendtner, James; Noy, Aleksandr; Chen, Chun-Long; De Yoreo, James J.

    2017-04-17

    Two-step nucleation pathways in which disordered, amorphous, or dense liquid states precede appearance of crystalline phases have been reported for a wide range of materials, but the dynamics of such pathways are poorly understood. Moreover, whether these pathways are general features of crystallizing systems or a consequence of system-specific structural details that select for direct vs two-step processes is unknown. Using atomic force microscopy to directly observe crystallization of sequence-defined polymers, we show that crystallization pathways are indeed sequence dependent. When a short hydrophobic region is added to a sequence that directly forms crystalline particles, crystallization instead follows a two-step pathway that begins with creation of disordered clusters of 10-20 molecules and is characterized by highly non-linear crystallization kinetics in which clusters transform into ordered structures that then enter the growth phase. The results shed new light on non-classical crystallization mechanisms and have implications for design of self-assembling polymer systems.

  1. Tuning crystallization pathways through sequence engineering of biomimetic polymers

    Science.gov (United States)

    Ma, Xiang; Zhang, Shuai; Jiao, Fang; Newcomb, Christina J.; Zhang, Yuliang; Prakash, Arushi; Liao, Zhihao; Baer, Marcel D.; Mundy, Christopher J.; Pfaendtner, James; Noy, Aleksandr; Chen, Chun-Long; de Yoreo, James J.

    2017-07-01

    Two-step nucleation pathways in which disordered, amorphous, or dense liquid states precede the appearance of crystalline phases have been reported for a wide range of materials, but the dynamics of such pathways are poorly understood. Moreover, whether these pathways are general features of crystallizing systems or a consequence of system-specific structural details that select for direct versus two-step processes is unknown. Using atomic force microscopy to directly observe crystallization of sequence-defined polymers, we show that crystallization pathways are indeed sequence dependent. When a short hydrophobic region is added to a sequence that directly forms crystalline particles, crystallization instead follows a two-step pathway that begins with the creation of disordered clusters of 10-20 molecules and is characterized by highly non-linear crystallization kinetics in which clusters transform into ordered structures that then enter the growth phase. The results shed new light on non-classical crystallization mechanisms and have implications for the design of self-assembling polymer systems.

  2. Characterization of a nonclassical class I MHC gene in a reptile, the Galapagos marine iguana (Amblyrhynchus cristatus.

    Directory of Open Access Journals (Sweden)

    Scott Glaberman

    Full Text Available Squamates are a diverse order of vertebrates, representing more than 7,000 species. Yet, descriptions of full-length major histocompatibility complex (MHC genes in this group are nearly absent from the literature, while the number of MHC studies continues to rise in other vertebrate taxa. The lack of basic information about MHC organization in squamates inhibits investigation into the relationship between MHC polymorphism and disease, and leaves a large taxonomic gap in our understanding of amniote MHC evolution. Here, we use both cDNA and genomic sequence data to characterize a class I MHC gene (Amcr-UA from the Galápagos marine iguana, a member of the squamate subfamily Iguaninae. Amcr-UA appears to be functional since it is expressed in the blood and contains many of the conserved peptide-binding residues that are found in classical class I genes of other vertebrates. In addition, comparison of Amcr-UA to homologous sequences from other iguanine species shows that the antigen-binding portion of this gene is under purifying selection, rather than balancing selection, and therefore may have a conserved function. A striking feature of Amcr-UA is that both the cDNA and genomic sequences lack the transmembrane and cytoplasmic domains that are necessary to anchor the class I receptor molecule into the cell membrane, suggesting that the product of this gene is secreted and consequently not involved in classical class I antigen-presentation. The truncated and conserved character of Amcr-UA lead us to define it as a nonclassical gene that is related to the few available squamate class I sequences. However, phylogenetic analysis placed Amcr-UA in a basal position relative to other published classical MHC genes from squamates, suggesting that this gene diverged near the beginning of squamate diversification.

  3. Characterization of SLCO5A1/OATP5A1, a solute carrier transport protein with non-classical function.

    Directory of Open Access Journals (Sweden)

    Katrin Sebastian

    Full Text Available Organic anion transporting polypeptides (OATP/SLCO have been identified to mediate the uptake of a broad range of mainly amphipathic molecules. Human OATP5A1 was found to be expressed in the epithelium of many cancerous and non-cancerous tissues throughout the body but protein characterization and functional analysis have not yet been performed. This study focused on the biochemical characterization of OATP5A1 using Xenopus laevis oocytes and Flp-In T-REx-HeLa cells providing evidence regarding a possible OATP5A1 function. SLCO5A1 is highly expressed in mature dendritic cells compared to immature dendritic cells (∼6.5-fold and SLCO5A1 expression correlates with the differentiation status of primary blood cells. A core- and complex- N-glycosylated polypeptide monomer of ∼105 kDa and ∼130 kDa could be localized in intracellular membranes and on the plasma membrane, respectively. Inducible expression of SLCO5A1 in HeLa cells led to an inhibitory effect of ∼20% after 96 h on cell proliferation. Gene expression profiling with these cells identified immunologically relevant genes (e.g. CCL20 and genes implicated in developmental processes (e.g. TGM2. A single nucleotide polymorphism leading to the exchange of amino acid 33 (L→F revealed no differences regarding protein expression and function. In conclusion, we provide evidence that OATP5A1 might be a non-classical OATP family member which is involved in biological processes that require the reorganization of the cell shape, such as differentiation and migration.

  4. Molecular pathways

    DEFF Research Database (Denmark)

    Cox, Thomas R; Erler, Janine Terra

    2014-01-01

    that 45% of deaths in the developed world are linked to fibrotic disease. Fibrosis and cancer are known to be inextricably linked; however, we are only just beginning to understand the common and overlapping molecular pathways between the two. Here, we discuss what is known about the intersection...... of fibrosis and cancer, with a focus on cancer metastasis, and highlight some of the exciting new potential clinical targets that are emerging from analysis of the molecular pathways associated with these two devastating diseases. Clin Cancer Res; 20(14); 3637-43. ©2014 AACR....

  5. Non-Classical Measures of Investment Risk on the Market of Precious Non-Ferrous Metals Using the Methodology of Stable Distributions

    OpenAIRE

    Dominik Krezolek

    2012-01-01

    The aim of this article is to present some non-classical risk measures which are commonly used in financial investments, including investments in assets from the market of precious non-ferrous metals. The time series of log-returns of gold, silver, platinum and palladium prices are considered. To properly asses the investment risk the measures based on Value-at-Risk methodology have been used (the VaR estimation approach based on values from the tail of the distribution). Additionally, the me...

  6. Screening non-classical 21-hydroxylase gene deficiency from patients diagnosed as polycystic ovary syndrome by gene assay

    Directory of Open Access Journals (Sweden)

    Jie HU

    2016-04-01

    Full Text Available Objective  To screen non-classical 21-hydroxylase deficiency (NC-21OHD from patients diagnosed as polycystic ovary syndrome (PCOS by gene assay. Methods  Ninety-eight patients with PCOS were enrolled according to 2003 Rotterdam criteria from Department of Endocrinology, Tangdu Hospital of Fourth Military Medical University, and they were divided into three groups according to the modified Ferriman-Gallway (mF-G score as follows: group A with score 0-2; group B with score 3-5, and group C with score ≥6. Meanwhile, 30 healthy subjects from the Medical Center of the Hospital were recruited as control group. Peripheral blood of all subjects were collected for extracting DNA, the CYP21A2 gene were amplified by 5 pairs of specific primers, and then the PCR products were sequenced by Shanghai Sangon Co. The subjects would accept test for serum cortisol and adrenocorticotropic hormone (ACTH at 8:00am if their CYP21A2 was proved to be abnormal. Results  Thirty subjects of control group had no any defects in CYP21A2, but 5 of 98 patients with PCOS were proved to be deficient in CYP21A2, and the genotypes were V281L/920-921insT (P1, V281L/I230M (P2, V281L/Normal (P3, P4, P5, respectively, and all of them were heterozygous mutations. The incidences of NC-21OHD in group C and B were 28.6% and 3.3%, respectively. Genotype P1 had been identified to belong to NC-21OHD, which was consistent with its clinical phenotype. All genotypes P3, P4 and P5 belonged to carriers. But for P2, since I230M hadn't been reported in literature, the patient with V281L/I230M couldn't be classified now. Serum biochemical results showed that only in P1 the cortisol was close to the normal lower level, and ACTH was close to the normal upper limit of the reported level in the literature, and the remainders were all normal. Conclusions  Although PCOS and NC-21OHD are very similar in clinical manifestations, they are different completely in the pathogenesis and treatment. So it

  7. Composition-structure-property relationships for non-classical ionomer cements formulated with zinc-boron germanium-based glasses.

    Science.gov (United States)

    Zhang, Xiaofang; Werner-Zwanziger, Ulrike; Boyd, Daniel

    2015-04-01

    Non-classical ionomer glasses like those based on zinc-boron-germanium glasses are of special interest in a variety of medical applications owning to their unique combination of properties and potential therapeutic efficacy. These features may be of particular benefit with respect to the utilization of glass ionomer cements for minimally invasive dental applications such as the atruamatic restorative treatment, but also for expanded clinical applications in orthopedics and oral-maxillofacial surgery. A unique system of zinc-boron-germanium-based glasses (10 compositions in total) has been designed using a Design of Mixtures methodology. In the first instance, ionomer glasses were examined via differential thermal analysis, X-ray diffraction, and (11)B MAS NMR spectroscopy to establish fundamental composition - structure-property relationships for the unique system. Secondly, cements were synthesized based on each glass and handling characteristics (working time, Wt, and setting time, St) and compression strength were quantified to facilitate the development of both experimental and mathematical composition-structure-property relationships for the new ionomer cements. The novel glass ionomer cements were found to provide Wt, St, and compression strength in the range of 48-132 s, 206-602 s, and 16-36 MPa, respectively, depending on the ZnO/GeO2 mol fraction of the glass phase. A lower ZnO mol fraction in the glass phase provides higher glass transition temperature, higher N4 rate, and in combination with careful modulation of GeO2 mol fraction in the glass phase provides a unique approach to extending the Wt and St of glass ionomer cement without compromising (in fact enhancing) compression strength. The data presented in this work provide valuable information for the formulation of alternative glass ionomer cements for applications within and beyond the dental clinic, especially where conventional approaches to modulating working time and strength exhibit co

  8. Neuro-protective effects of CNTF on hippocampal neurons via an unknown signal transduction pathway

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    In our previous study, we proposed that there may be an unknown pathway in the upper stream of the known signal transduction pathway of Ciliary neurotrophic factor (CNTF) that mediates the neuro-protective function of CNTF. In the present experiment, we observed that the neuro-protective function of the non-classic signal transduction pathway in a L-NMDA (a glutamic acid ion type receptor atagonist) induced hippocampal neuron injury model, using primary culture rat hippocampal neurons, continuous photography and gp130 immunohistochemical assay. The results showed that L-NMDA induced injurious reaction of hippocampal neurons, and CNTF was able to inhibit the toxic action of L-NMDA on hippocampal neurons. Additionally, when JAK/STATs in the known classic signal transduction pathway of CNTF were blocked by PTPi-2, the protective effect of CNTF against L-NMDA injury still existed. L-NMDA caused a rapid increase in the concentration of hippocampal intracellular free [Ca2+]i. CNTF was able to attenuate L-NMDA-induced elevation of [Ca2+]i, and blocking JAK/STATs in the known classic signal trans- duction pathway of CNTF did not affect L-NMDA- induced elevation of [Ca2+]i, indicating that, apart from the known classic signal transduction pathway, there may be some other transduction pathways for CNTF to exert the protective effect on hippocampal neurons, and this pathway is related to [Ca2+].

  9. Nonclassical Vitamin D Actions

    Directory of Open Access Journals (Sweden)

    Armin Zittermann

    2010-03-01

    Full Text Available It is becoming increasingly clear that vitamin D has a broad range of actions in the human body. Besides its well-known effects on calcium/phosphate homeostasis, vitamin D influences muscle function, cardiovascular homeostasis, nervous function, and the immune response. Vitamin D deficiency/insufficiency has been associated with muscle weakness and a high incidence of various chronic diseases such as cardiovascular disease, cancer, multiple sclerosis, and type 1 and 2 diabetes. Most importantly, low vitamin D status has been found to be an independent predictor of all-cause mortality. Several recent randomized controlled trials support the assumption that vitamin D can improve muscle strength, glucose homeostasis, and cardiovascular risk markers. In addition, vitamin D may reduce cancer incidence and elevated blood pressure. Since the prevalence of vitamin D deficiency/insufficiency is high throughout the world, there is a need to improve vitamin D status in the general adult population. However, the currently recommended daily vitamin D intake of 5–15 µg is too low to achieve an adequate vitamin D status in individuals with only modest skin synthesis. Thus, there is a need to recommend a vitamin D intake that is effective for achieving adequate circulating 25-hydroxyvitamin D concentrations (>75 nmol/L.

  10. Designing pathways

    DEFF Research Database (Denmark)

    Scheuer, John Damm

    2010-01-01

    The theoretical background in this chapter is organizational studies and especially theories about design and design processes in organizations. The concept of design is defined as a particular kind of work aimed at making arrangements in order to change existing situations into desired ones....... The illustrative case example is the introduction of clinical pathways in a psychiatric department. The contribution to a general core of design research is the development of the concept of design work and a critical discussion of the role of technological rules in design work....

  11. Designing pathways

    DEFF Research Database (Denmark)

    2010-01-01

    The theoretical background in this chapter is organizational studies and especially theories about design and design processes in organizations. The concept of design is defined as a particular kind of work aimed at making arrangements in order to change existing situations into desired ones....... The illustrative case example is the introduction of clinical pathways in a psychiatric department. The contribution to a general core of design research is the development of the concept of design work and a critical discussion of the role of technological rules in design work....

  12. Pathway collages: personalized multi-pathway diagrams.

    Science.gov (United States)

    Paley, Suzanne; O'Maille, Paul E; Weaver, Daniel; Karp, Peter D

    2016-12-13

    Metabolic pathway diagrams are a classical way of visualizing a linked cascade of biochemical reactions. However, to understand some biochemical situations, viewing a single pathway is insufficient, whereas viewing the entire metabolic network results in information overload. How do we enable scientists to rapidly construct personalized multi-pathway diagrams that depict a desired collection of interacting pathways that emphasize particular pathway interactions? We define software for constructing personalized multi-pathway diagrams called pathway-collages using a combination of manual and automatic layouts. The user specifies a set of pathways of interest for the collage from a Pathway/Genome Database. Layouts for the individual pathways are generated by the Pathway Tools software, and are sent to a Javascript Pathway Collage application implemented using Cytoscape.js. That application allows the user to re-position pathways; define connections between pathways; change visual style parameters; and paint metabolomics, gene expression, and reaction flux data onto the collage to obtain a desired multi-pathway diagram. We demonstrate the use of pathway collages in two application areas: a metabolomics study of pathogen drug response, and an Escherichia coli metabolic model. Pathway collages enable facile construction of personalized multi-pathway diagrams.

  13. Synthesis of New 2-Halo-2-(1H-tetrazol-5-yl-2H-azirines via a Non-Classical Wittig Reaction

    Directory of Open Access Journals (Sweden)

    Ana L. Cardoso

    2015-12-01

    Full Text Available The synthesis and reactivity of tetrazol-5-yl-phosphorus ylides towards N-halosuccinimide/TMSN3 reagent systems was explored, opening the way to new haloazidoalkenes bearing a tetrazol-5-yl substituent. These compounds were obtained as single isomers, except in one case. X-ray crystal structures were determined for three derivatives, establishing that the non-classical Wittig reaction leads to the selective synthesis of haloazidoalkenes with (Z-configuration. The thermolysis of the haloazidoalkenes afforded new 2-halo-2-(tetrazol-5-yl-2H-azirines in high yields. Thus, the reported synthetic methodologies gave access to important building blocks in organic synthesis, vinyl tetrazoles and 2-halo-2-(tetrazol-5-yl-2H-azirine derivatives.

  14. Аsymptotic solution of a class thermoelasticity nonclassical boundary value problems for the package of an orthotropic plate of variable thickness

    Directory of Open Access Journals (Sweden)

    Aghalovyan M.L.

    2014-03-01

    Full Text Available We solve the non-classical boundary value problem for an orthotropic packet when on one of its front surface the corresponding components of the stress tensor are equal to zero and sets the value of the displacement vector. The task, in particular, is modeling the behavior of the lithospheric plates of the Earth, or a specific region of the earth's crust subject to tectonic movements of the fixed seismic stations, GPS and other measuring instruments. On the basis of three-dimensional equations of thermo-elasticity asymptotic method derived recurrence equations allow for a package of orthotropic layers of varying thickness. We derive recursive formulas for determining the components of the stress tensor and the displacement vector.

  15. SSZ-13 Crystallization by Particle Attachment and Deterministic Pathways to Crystal Size Control.

    Science.gov (United States)

    Kumar, Manjesh; Luo, Helen; Román-Leshkov, Yuriy; Rimer, Jeffrey D

    2015-10-14

    Many synthetic and natural crystalline materials are either known or postulated to grow via nonclassical pathways involving the initial self-assembly of precursors that serve as putative growth units for crystallization. Elucidating the pathway(s) by which precursors attach to crystal surfaces and structurally rearrange (postattachment) to incorporate into the underlying crystalline lattice is an active and expanding area of research comprising many unanswered fundamental questions. Here, we examine the crystallization of SSZ-13, which is an aluminosilicate zeolite that possesses exceptional physicochemical properties for applications in separations and catalysis (e.g., methanol upgrading to chemicals and the environmental remediation of NO(x)). We show that SSZ-13 grows by two concerted mechanisms: nonclassical growth involving the attachment of amorphous aluminosilicate particles to crystal surfaces and classical layer-by-layer growth via the incorporation of molecules to advancing steps on the crystal surface. A facile, commercially viable method of tailoring SSZ-13 crystal size and morphology is introduced wherein growth modifiers are used to mediate precursor aggregation and attachment to crystal surfaces. We demonstrate that small quantities of polymers can be used to tune crystal size over 3 orders of magnitude (0.1-20 μm), alter crystal shape, and introduce mesoporosity. Given the ubiquitous presence of amorphous precursors in a wide variety of microporous crystals, insight of the SSZ-13 growth mechanism may prove to be broadly applicable to other materials. Moreover, the ability to selectively tailor the physical properties of SSZ-13 crystals through molecular design offers new routes to optimize their performance in a wide range of commercial applications.

  16. The Presence of Clitoromegaly in the Nonclassical Form of 21-Hydroxylase Deficiency Could Be Partially Modulated by the CAG Polymorphic Tract of the Androgen Receptor Gene

    Science.gov (United States)

    Garcia Gomes, Larissa; Bugano Diniz Gomes, Diogo; Marcondes, José Antônio Miguel; Madureira, Guiomar; de Mendonca, Berenice Bilharinho; Bachega, Tânia A. Sartori Sanchez

    2016-01-01

    Background In the nonclassical form (NC), good correlation has been observed between genotypes and 17OH-progesterone (17-OHP) levels. However, this correlation was not identified with regard to the severity of hyperandrogenic manifestations, which could depend on interindividual variability in peripheral androgen sensitivity. Androgen action is modulated by the polymorphic CAG tract (nCAG) of the androgen receptor (AR) gene and by polymorphisms in 5α-reductase type 2 (SRD5A2) enzyme, both of which are involved in the severity of hyperandrogenic disorders. Objectives To analyze whether nCAG-AR and SRD5A2 polymorphisms influence the severity of the nonclassical phenotype. Patients NC patients (n = 114) diagnosed by stimulated-17OHP ≥10 ng/mL were divided into groups according to the beginning of hyperandrogenic manifestations (pediatric and adolescent/adult) and CYP21A2 genotypes (C/C: homozygosis for mild mutations; A/C: compound heterozygosis for severe/mild mutations). Methods CYP21A2 mutations were screened by allelic-specific PCR, MLPA and/or sequencing. HpaII-digested and HpaII-undigested DNA samples underwent GeneScan analysis to study nCAG, and the SRD5A2 polymorphisms were screened by RLFP. Results Mean nCAG did not differ among pediatric, adolescent/adult and asymptomatic subjects. In the C/C genotype, we observed a significantly lower frequency of longer CAG alleles in pediatric patients than in adolescent/adults (p = 0.01). In patients carrying the A/C genotype, the frequencies of shorter and longer CAG alleles did not differ between pediatric patients and adolescent/adults (p>0.05). Patients with clitoromegaly had significantly lower weighted CAG biallelic mean than those without it: 19.1±2.7 and 21.6±2.5, respectively (p = 0.007), independent of the CYP21A2 genotype's severity. The SRD5A2 polymorphisms were not associated with the variability of hyperandrogenic NC phenotypes. Conclusions In this series, we observed a modulatory effect of the CAG

  17. Airship Observations of Formaldehyde in the Po Valley as a Probe of Boundary Layer Development and Non-Classical Radical Chemistry

    Science.gov (United States)

    Kaiser, J.; Wolfe, G. M.; Keutsch, F. N.

    2012-12-01

    Stagnant meteorological conditions and high anthropogenic emissions make the Po Valley in Northern Italy one of Europe's most polluted regions. Understanding the processes controlling ozone production in this environment is essential for developing effective mitigation strategies. As both a source of HO2 radicals and an intermediate in the oxidation of most volatile organic compounds (VOCs), formaldehyde (HCHO) is a useful tracer for the oxidative processing of hydrocarbons that leads to ozone production. During the Pan-European Gas-AeroSOls Climate Interaction Study (PEGASOS), HCHO measurements were acquired via a Fiber Laser-Induced Fluorescence (FiLIF) instrument onboard a Zeppelin airship. This mission represents the first successful airborne deployment of the FiLIF instrument. With low flight speeds and vertical profiling capabilities, these Zeppelin-based observations in conjunction with other measurements may offer new insights into the spatial and temporal variability of atmospheric composition within the Po Valley region. Preliminary comparisons of modeled and measured HCHO concentrations at various altitudes and VOC/NOx regimes will be presented. Analysis will focus on 1) the transition from nocturnal to daytime boundary layers, and 2) the potential role of "non-classical" radical chemistry in ozone production.

  18. Convective storms and non-classical low-level jets during high ozone level episodes in the Amazon region: An ARM/GOAMAZON case study

    Science.gov (United States)

    Dias-Junior, Cléo Q.; Dias, Nelson Luís; Fuentes, José D.; Chamecki, Marcelo

    2017-04-01

    In this work, we investigate the ozone dynamics during the occurrence of both downdrafts associated with mesoscale convective storms and non-classical low-level jets. Extensive data sets, comprised of air chemistry and meteorological observations made in the Amazon region of Brazil over the course of 2014-15, are analyzed to address several questions. A first objective is to investigate the atmospheric thermodynamic and dynamic conditions associated with storm-generated ozone enhancements in the Amazon region. A second objective is to determine the magnitude and the frequency of ground-level ozone enhancements related to low-level jets. Ozone enhancements are analyzed as a function of wind shear, low-level jet maximum wind speed, and altitude of jet core. Strong and sudden increases in ozone levels are associated with simultaneous changes in variables such as horizontal wind speed, convective available potential energy, turbulence intensity and vertical velocity skewness. Rapid increases in vertical velocity skewness give support to the hypothesis that the ozone enhancements are directly related to downdrafts. Low-level jets associated with advancing density currents are often present during and after storm downdrafts that transport ozone-enriched air from aloft to the surface.

  19. A case of recurrent labial adhesions in a 15-month-old child with asymptomatic non-classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

    Science.gov (United States)

    Janus, Dominika; Wojcik, Malgorzata; Malunowicz, Ewa; Starzyk, Jerzy B

    2012-01-01

    Labial adhesions (synechia vulvae) are a relatively common disorder of the external genitalia in prepubertal girls. They usually occur between 3 months and 6 years of age, with a peak between 13 and 23 months of life. In the majority of cases, labial adhesions are asymptomatic and noticed by the parents or a physician during a routine physical examination. Frequently, they cause recurrent urinary tract infections. This report presents the case of a 15-month-old girl with recurrent labial adhesions and urinary tract infections. She was followed-up by a urologist from the age of 3 months, treated topically (estriol cream 1 mg/g and emollients) and surgically. No signs of androgenization were seen apart from advanced bone age. Urinary steroid profile and molecular analysis confirmed the diagnosis of non-classic congenital adrenal hyperplasia (NCCAH) due to 21-hydroxylase deficiency. In the described case, a coincidence of NCCAH and labial adhesion cannot be excluded particularly in view of the resolving of urinary tract infections at the same time as resolving of labial adhesions. However, it seems that in cases of recurrent labial adhesion/synechia that require repeated surgical interventions in view of ineffectiveness of conservative treatment - as it was observed in the presented case - one should consider searching for NCCAH. This may allow not only for the causal treatment of labial adhesions but, above all, NCCAH and, in consequence, the prevention of intensification of virilization, hirsutism, menstrual cycle, and fertility disturbances that are observed starting from puberty.

  20. Theoretical Study of Nonclassical Platinum Complexes Bonding to Purine Bases: How the Long-lived Monofunctional Adducts Can Be in Existence?

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The B3LYP/6-31G* level of theory was used for the optimization of nonclassical platinum drugs with planar aromatic heterocycle ligands in addition to their monoaqua species, diaqua species and monofunctional adducts. Single point calculations were performed on optimized geometries using the MP2/6-31G** method, and the Lanl2dz pseudo potential for the Pt atom remained constant in all calculations. It can be easily seen that the trans effect can influence both geometrical structures and bond dissociating energies (BDEs). On the basis of our calculation, we get that the long-lived monofunctional adducts with chloride ligand may be in existence, because they possessed higher stability energies, easily dissociated chloride compared with the monoaqua species dissociating chloride and that replacement of the first chloride by bases became exothermic in solution. Our calculated results also demonstrate that the strongest H-bonds appear in the complexes of q-wG and t-wG using different methods. In comparison with adenine complexes, the corresponding guanine complexes possess larger interaction energies as well as higher stability energies either corrected by basis set superposition error (bsse) of Boys-Bernardi counterpoise method or uncorrected both in gas phase and in solution with one exception that the stability energy of q-ClA complex in solution is larger than that of q-ClG complex. Finally, the nature of bond was analyzed in terms of partial charges distribution based on NBO population.

  1. Classical and Non-Classical Roles for Pre-Receptor Control of DHT Metabolism in Prostate Cancer Progression.

    Science.gov (United States)

    Zhang, Ailin; Zhang, Jiawei; Plymate, Stephen; Mostaghel, Elahe A

    2016-04-01

    Androgens play an important role in prostate cancer (PCa) development and progression. Accordingly, androgen deprivation therapy remains the front-line treatment for locally recurrent or advanced PCa, but patients eventually relapse with the lethal form of the disease termed castration resistant PCa (CRPC). Importantly, castration does not eliminate androgens from the prostate tumor microenvironment which is characterized by elevated tissue androgens that are well within the range capable of activating the androgen receptor (AR). In this mini-review, we discuss emerging data that suggest a role for the enzymes mediating pre-receptor control of dihydrotestosterone (DHT) metabolism, including AKR1C2, HSD17B6, HSD17B10, and the UGT family members UGT2B15 and UGT2B17, in controlling intratumoral androgen levels, and thereby influencing PCa progression. We review the expression of steroidogenic enzymes involved in this pathway in primary PCa and CRPC, the activity and regulation of these enzymes in PCa experimental models, and the impact of genetic variation in genes mediating pre-receptor DHT metabolism on PCa risk. Finally, we discuss recent data that suggests several of these enzymes may also play an unrecognized role in CRPC progression separate from their role in androgen inactivation.

  2. Processing and MHC class II presentation of exogenous soluble antigen involving a proteasome-dependent cytosolic pathway in CD40-activated B cells.

    Science.gov (United States)

    Becker, Hans Jiro; Kondo, Eisei; Shimabukuro-Vornhagen, Alexander; Theurich, Sebastian; von Bergwelt-Baildon, Michael S

    2016-08-01

    Activated B cells have the capacity to present antigen and induce immune responses as potent antigen-presenting cells (APCs). As in other APCs, antigen presentation by B cells involves antigen internalization, antigen processing, and peptide loading onto MHC molecules. However, while the mechanism of antigen processing has been studied extensively in other APCs, this pathway remains elusive in B cells. The aim of this study was to investigate the MHC class II processing pathway in CD40-activated B cells (CD40Bs), as a model for activated, antigen-presenting B cells. Using CMV pp65 as a model antigen, we evaluated processing and presentation of the CD4 + T-cell epitope 509-523 (K509) by human CD40Bs in ELISPOT assays. As expected, stimulation of specific CD4 + T-cell clones was attenuated after pretreatment of CD40Bs with inhibitors of classic class II pathway components. However, proteasome inhibitors such as epoxomicin limited antigen presentation as well. This suggests that the antigen is processed in a non-classical, cytosolic MHC class II pathway. Further experiments with truncated protein variants revealed involvement of the proteasome in processing of the N and C extensions of the epitope. Access to the cytosol was shown to be size dependent. Epoxomicin sensitivity exclusively in CD40B cells, but not in dendritic cells, suggests a novel processing mechanism unique to this APC. Our data suggest that B cells process antigen using a distinct, non-classical class II pathway.

  3. Structural Basis for Dual-Inhibition Mechanism of a Non-Classical Kazal-Type Serine Protease Inhibitor from Horseshoe Crab in Complex with Subtilisin

    Energy Technology Data Exchange (ETDEWEB)

    Shenoy, Rajesh T. [National Univ. of Singapore (Singapore); Thangamani, Saravanan [National Univ. of Singapore (Singapore); Univ. of Texas Medical Branch, Galveston, TX (United States); Velazquez-Campoy, Adrian [Univ. of Zaragoza (Spain); Ho, Bow [National Univ. of Singapore (Singapore); Ding, Jeak Ling [National Univ. of Singapore (Singapore); Sivaraman, J. [National Univ. of Singapore (Singapore); Kursula, Petri [Univ. of Oulu (Germany)

    2011-04-26

    Serine proteases play a crucial role in host-pathogen interactions. In the innate immune system of invertebrates, multi-domain protease inhibitors are important for the regulation of host-pathogen interactions and antimicrobial activities. Serine protease inhibitors, 9.3-kDa CrSPI isoforms 1 and 2, have been identified from the hepatopancreas of the horseshoe crab, Carcinoscorpius rotundicauda. The CrSPIs were biochemically active, especially CrSPI-1, which potently inhibited subtilisin (Ki=1.43 nM). CrSPI has been grouped with the non-classical Kazal-type inhibitors due to its unusual cysteine distribution. Here we report the crystal structure of CrSPI-1 in complex with subtilisin at 2.6 Å resolution and the results of biophysical interaction studies. The CrSPI-1 molecule has two domains arranged in an extended conformation. These two domains act as heads that independently interact with two separate subtilisin molecules, resulting in the inhibition of subtilisin activity at a ratio of 1:2 (inhibitor to protease). Each subtilisin molecule interacts with the reactive site loop from each domain of CrSPI-1 through a standard canonical binding mode and forms a single ternary complex. In addition, we propose the substrate preferences of each domain of CrSPI-1. Domain 2 is specific towards the bacterial protease subtilisin, while domain 1 is likely to interact with the host protease, Furin. Elucidation of the structure of the CrSPI-1: subtilisin (1:2) ternary complex increases our understanding of host-pathogen interactions in the innate immune system at the molecular level and provides new strategies for immunomodulation.

  4. Nonclassical effects of a two-level spin system interacting with a two-mode cavity field via two-photon transition.

    Science.gov (United States)

    Grinberg, Horacio

    2008-12-18

    The interaction of a two-level cyclic XY n-spin model with a two-mode cavity field involving two-photon transitions is investigated through a generalized Jaynes-Cummings model in the rotating-wave approximation. The two-photon interacting Hamiltonian becomes from the replacement of each single-mode field in the one-photon interacting Hamiltonian with the second-harmonic generation. It was assumed that initially the correlated field modes are in disentangled coherent states having the same photon distribution and that the spin system is in an excited state. At any time t > 0, the spin system and the field are in an entangled state, in this case, via a unitary time evolution operator. Thus, the spontaneous decay of a spin level was treated by considering the interaction of the two-level spin system with the modes of the universe in the vacuum state. The different cases of interest, characterized in terms of a detuning parameter for each mode, which emerge from nonvanishing commutation relations, were analytically implemented and numerically discussed for various values of the initial mean photon number and spin-photon coupling constants. Photon distribution, time evolution of the spin population inversion, as well as the statistical properties of the field leading to the possible production of nonclassical states, such as antibunched light, violations of the Cauchy-Schwartz inequality, and second- and fourth-order squeezing, are examined. The case of zero detuning of both modes was treated in terms of a linearization of the expansion of the time evolution operator, while in other three cases, the computations were conducted via second- and third-order Dyson perturbation expansion of the time evolution operator matrix elements for the excited and ground states of the spin system, respectively.

  5. Galectin-3 is a non-classic RNA binding protein that stabilizes the mucin MUC4 mRNA in the cytoplasm of cancer cells

    Science.gov (United States)

    Coppin, Lucie; Vincent, Audrey; Frénois, Frédéric; Duchêne, Belinda; Lahdaoui, Fatima; Stechly, Laurence; Renaud, Florence; Villenet, Céline; Seuningen, Isabelle Van; Leteurtre, Emmanuelle; Dion, Johann; Grandjean, Cyrille; Poirier, Françoise; Figeac, Martin; Delacour, Delphine; Porchet, Nicole; Pigny, Pascal

    2017-01-01

    Pancreatic cancer cells express high levels of MUC1, MUC4 and MUC16 mRNAs that encode membrane-bound mucins. These mRNAs share unusual features such as a long half-life. However, it remains unknown how mucin mRNA stability is regulated. Galectin-3 (Gal-3) is an endogenous lectin playing important biological functions in epithelial cells. Gal-3 is encoded by LGALS3 which is up-regulated in pancreatic cancer. Despite the absence of a RNA-recognition motif, Gal-3 interacts indirectly with pre-mRNAs in the nucleus and promotes constitutive splicing. However a broader role of Gal-3 in mRNA fate is unexplored. We report herein that Gal-3 increases MUC4 mRNA stability through an intermediate, hnRNP-L which binds to a conserved CA repeat element in the 3′UTR in a Gal-3 dependent manner and also controls Muc4 mRNA levels in epithelial tissues of Gal3−/− mice. Gal-3 interacts with hnRNP-L in the cytoplasm, especially during cell mitosis, but only partly associates with protein markers of P-Bodies or Stress Granules. By RNA-IP plus RNA-seq analysis and imaging, we demonstrate that Gal-3 binds to mature spliced MUC4 mRNA in the perinuclear region, probably in hnRNP-L-containing RNA granules. Our findings highlight a new role for Gal-3 as a non-classic RNA-binding protein that regulates MUC4 mRNA post-transcriptionally. PMID:28262838

  6. Drug Design Targeting the CXCR4/CXCR7/CXCL12 Pathway.

    Science.gov (United States)

    Xu, Dongsheng; Li, Rongshi; Wu, Jianguo; Jiang, Li; Zhong, Haizhen A

    2016-01-01

    Under physiological conditions, CXCL12 modulates cell proliferation, survival, angiogenesis, and migration mainly through CXCR4. Interestingly, the newly discovered receptor CXCR7 for CXCL12 is highly expressed in many tumor cells as well as tumor-associated blood vessels, although the level of CXCR7 in normal blood cells is low. Recently, many studies have suggested that CXCR7 promotes cell growth and metastasis in various cancers, including lymphoma and leukemia, hepatocecullar, ovarian, colorectal, breast and lung cancer. Compared to CXCR4, CXCR7 is a non-classical GPCR that is unable to activate G proteins. The function of CXCR7 is generally considered to be mediated by: (a) recruiting β-arrestin-2; (b) heterodimerizing with CXCR4; and (c) acting as a "scavenger" of CXCL12, thus lowering the level of CXCL12 to weaken the activity of CXCR4. However, the crosstalk between CXCL12/CXCR7/CXCR4 and other signaling pathways (such as the p38 MAPK pathway, the PI3K/mTOR pathway, the STAT3 signaling, and metalloproteinases MMP-9 and MMP-2) is more complicated. The function of CXCR7 is also involved in modulating tumor microenvironment, tumor cell migration and apoptosis. Understanding these complex interactions will provide insight in drug design targeting the CXCR7 as potential anticancer therapy.

  7. Non-classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency revisited: an update with a special focus on adolescent and adult women.

    Science.gov (United States)

    Carmina, Enrico; Dewailly, Didier; Escobar-Morreale, Héctor F; Kelestimur, Fahrettin; Moran, Carlos; Oberfield, Sharon; Witchel, Selma F; Azziz, Ricardo

    2017-09-01

    Non-classic congenital hyperplasia (NCAH) due to 21-hydroxylase deficiency is a common autosomal recessive disorder characterized by androgen excess. We conducted a systematic review and critical assessment of the available evidence pertaining to the epidemiology, pathophysiology, diagnosis and management of NCAH. A meta-analysis of epidemiological data was also performed. Peer-reviewed studies evaluating NCAH published up to October 2016 were reviewed. Multiple databases were searched including MEDLINE, EMBASE, Cochrane, ERIC, EBSCO, dissertation abstracts, and current contents. The worldwide prevalence of NCAH amongst women presenting with signs and symptoms of androgen excess is 4.2% (95% confidence interval: 3.2-5.4%). The clinical consequences of NCAH expand from infancy, i.e. accelerated growth, to adolescence and adulthood, i.e. premature pubarche, cutaneous symptoms and oligo-ovulation in a polycystic ovary syndrome (PCOS)-like clinical picture. The diagnosis of NCAH relies on serum 17-hydroxyprogesterone (17-OHP) concentrations. A basal 17-OHP concentration ≥2 ng/ml (6 nmol/l) should be used for screening if more appropriate in-house cut-off values are not available. Definitive diagnosis requires a 17-OHP concentration ≥10 ng/ml (30 nmol/l), either basally or after cosyntropin-stimulation. Molecular genetic analysis of the CYP21A2 gene, which is responsible for 21-hydroxylase activity, may be used for confirmation purposes and should be offered to all patients with NCAH along with genetic counseling because these patients frequently carry alleles that may result in classic CAH, the more severe form of the disease, in their progeny. Treatment must be individualized. Glucocorticoid replacement therapy may benefit pediatric patients with accelerated growth or advanced bone age or adult women seeking fertility, whereas adequate control of menstrual irregularity, hirsutism and other cutaneous symptoms is best served by the use of oral contraceptive pills

  8. Classic and non-classic 21-hydroxylase deficiency can be discriminated from P450 oxidoreductase deficiency in Japanese infants by urinary steroid metabolites

    Science.gov (United States)

    Koyama, Yuhei; Homma, Keiko; Fukami, Maki; Miwa, Masayuki; Ikeda, Kazushige; Ogata, Tsutomu; Murata, Mitsuru; Hasegawa, Tomonobu

    2016-01-01

    Abstract. We previously reported a two-step biochemical diagnosis to discriminate classic 21-hydroxylase deficiency (C21OHD) from P450 oxidoreductase deficiency (PORD) by using urinary steroid metabolites: the pregnanetriolone/tetrahydrocortisone ratio (Ptl / the cortisol metabolites 5α- and 5β-tetrahydrocortisone (sum of these metabolites termed THEs), and 11β-hydroxyandrosterone (11OHAn). The objective of this study was to investigate whether both C21OHD and non-classic 21OHD (C+NC21OHD) could be biochemically differentiated from PORD. We recruited 55 infants with C21OHD, 8 with NC21OHD, 16 with PORD, 57 with transient hyper-17α-hydroxyprogesteronemia (TH17OHP), and 2,473 controls. All infants were Japanese with ages between 0–180 d. In addition to Ptl, THEs, and 11OHAn, we measured urinary tetrahydroaldosterone (THAldo) and pregnenediol (PD5). The first step: by Ptl with the age-specific cutoffs 0.06 mg/g creatinine (0–10 d of age) and 0.3 mg/g creatinine (11–180 d of age), we were able to differentiate C+NC21OHD and PORD from TH17OHP and controls (0–10 d of age: 0.065–31 vs. < 0.001–0.052, 11–180 d of age: 0.40–42 vs. < 0.001–0.086) with 100% sensitivity and specificity. The second step: by the 11OHAn/THAldo or 11OHAn/PD5 ratio with a cutoff of 0.80 or 1.0, we were able to discriminate between C+NC21OHD and PORD (1.0–720 vs. 0.021–0.61 or 1.8–160 vs. 0.005–0.32, respectively) with 100% sensitivity and specificity. Ptl, 11OHAn/THAldo, and 11OHAn/PD5 could differentiate between C+NC21OHD and PORD in Japanese infants. PMID:27212795

  9. Novel Systematics of Nomenclature and Classification of Female Functional Androgenization (Including Polycystic Ovary Syndrome and Non-Classic Congenital Adrenal Hyperplasia

    Directory of Open Access Journals (Sweden)

    Geisthövel F

    2010-01-01

    Full Text Available Objective: A novel nomenclature as well as a comprehensive, clearly defined classification of functional androgenization (FA from puberty well into postmenopause have been developed. Data are presented indicating the applicability of this algorithm. Design: Retrospective case-control study involving FA-patients, and controls (C. Methods: FA-patients were classified into five groups, functional cutaneous androgenization (FCA: skin as well as functional androgenizing syndrome (FAS I (ovary, II (adrenal, III (multi-organ-disorder with FA, obesity, hyperinsulinaemia and IV (residual FA dysfunctions using group-specific variable clusters. They are set up by primary (classifying variables such as cutaneous androgenetic symptoms (acne vulgaris, hirsutism, androgenetic alopecia, body mass index (BMI, testosterone, free androgen index (FAI, polyfollicular ovaries (PFOs, and 1-h-insulin (after oral glucose loading. Groups FCA and FAS I–III were sub-classified through classic full-blown (“a” and non-classic, minimum standard core/miscellaneous clusters (“b”. Variables were allocated as integral part of different clusters (e.g. enhanced BMI: in FCAb, FAS IIb, FAS IIIa/b, and FAS IV. Patients’ complete characterization was achieved additionally by using secondary (facultative variables, e.g. triglycerid levels. Results: The FA-groups included 6, 33, 10, 59, and 18 subjects. All FCA-patients presented cutaneous androgenetic symptoms, PFOs were visualized in all FAS I and III patients. Group FAS Ia showed highest LH levels, and testosterone was higher in FAS I vs. FCA, FAS II, FAS IV and C. Levels of DHEAS were found to be highest in group FAS II. BMI and triglycerids were higher in FAS III vs. FCA, FAS I, FAS II, and C, and one-hr-insulin in FAS III was higher vs. FCA, FAS I, and C. In FAS IV covering the residual FA-patients, several obese, hyperinsulinaemic individuals were classified who showed an increased FAI without the presence of PFOs

  10. Nonclassical radiation from diamond nanocrystals

    CERN Document Server

    Beveratos, A; Gacoin, T; Poizat, J P; Grangier, P; Beveratos, Alexios; Brouri, Rosa; Gacoin, Thierry; Poizat, Jean-Philippe; Grangier, Philippe

    2001-01-01

    The quantum properties of the fluorescence light emitted by diamond nanocrystals containing a single nitrogen-vacancy (NV) colored center is investigated. We have observed photon antibunching with very low background light. This system is therefore a very good candidate for the production of single photon on demand. In addition, we have measured larger NV center lifetime in nanocrystals than in the bulk, in good agreement with a simple quantum electrodynamical model.

  11. Higher dimensional nonclassical eigenvalue asymptotics

    Science.gov (United States)

    Camus, Brice; Rautenberg, Nils

    2015-02-01

    In this article, we extend Simon's construction and results [B. Simon, J. Funct. Anal. 53(1), 84-98 (1983)] for leading order eigenvalue asymptotics to n-dimensional Schrödinger operators with non-confining potentials given by Hn α = - Δ + ∏ i = 1 n |x i| α i on ℝn (n > 2), α ≔ ( α 1 , … , α n ) ∈ ( R+ ∗ ) n . We apply the results to also derive the leading order spectral asymptotics in the case of the Dirichlet Laplacian -ΔD on domains Ωn α = { x ∈ R n : ∏ j = 1 n }x j| /α j α n < 1 } .

  12. Advancements in nonclassical gas dynamics

    NARCIS (Netherlands)

    Nannan , N. R.

    2009-01-01

    Shock waves can be formed in all states of matter, be it in the single- or multi-phase condition, when the substance is subjected to a rapid change of state, e.g., a sudden pressure variation. In the case of shock waves in vapors and gases, because of the fact that the developed theory is often

  13. DMPD: Regulatory pathways in inflammation. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17967718 Regulatory pathways in inflammation. Mantovani A, Garlanda C, Locati M, Ro....html) (.csml) Show Regulatory pathways in inflammation. PubmedID 17967718 Title Regulatory pathways in infl

  14. Pathway Commons, a web resource for biological pathway data.

    Science.gov (United States)

    Cerami, Ethan G; Gross, Benjamin E; Demir, Emek; Rodchenkov, Igor; Babur, Ozgün; Anwar, Nadia; Schultz, Nikolaus; Bader, Gary D; Sander, Chris

    2011-01-01

    Pathway Commons (http://www.pathwaycommons.org) is a collection of publicly available pathway data from multiple organisms. Pathway Commons provides a web-based interface that enables biologists to browse and search a comprehensive collection of pathways from multiple sources represented in a common language, a download site that provides integrated bulk sets of pathway information in standard or convenient formats and a web service that software developers can use to conveniently query and access all data. Database providers can share their pathway data via a common repository. Pathways include biochemical reactions, complex assembly, transport and catalysis events and physical interactions involving proteins, DNA, RNA, small molecules and complexes. Pathway Commons aims to collect and integrate all public pathway data available in standard formats. Pathway Commons currently contains data from nine databases with over 1400 pathways and 687,000 interactions and will be continually expanded and updated.

  15. Clinical Pathway for Thyroidectomy.

    Science.gov (United States)

    Villar del Moral, Jesús María; Soria Aledo, Víctor; Colina Alonso, Alberto; Flores Pastor, Benito; Gutiérrez Rodríguez, María Teresa; Ortega Serrano, Joaquín; Parra Hidalgo, Pedro; Ros López, Susana

    2015-05-01

    Clinical pathways are care plans applicable to patient care procedures that present variations in practice and a predictable clinical course. They are designed not as a substitute for clinical judgment, but rather as a means to improve the effectiveness and efficiency of the procedures. This clinical pathway is the result of a collaborative work of the Sections of Endocrine Surgery and Quality Management of the Spanish Association of Surgeons. It attempts to provide a framework for standardizing the performance of thyroidectomy, the most frequently performed operation in endocrine surgery. Along with the usual documents of clinical pathways (temporary matrix, variance tracking and information sheets, assessment indicators and a satisfaction questionnaire) it includes a review of the scientific evidence around different aspects of pre, intra and postoperative management. Among others, antibiotic and antithrombotic prophylaxis, preoperative preparation in hyperthyroidism, intraoperative neuromonitoring and systems for obtaining hemostasis are included, along with management of postoperative hypocalcemia.

  16. Pathway analysis of IMC

    DEFF Research Database (Denmark)

    Skrypnyuk, Nataliya; Nielson, Flemming; Pilegaard, Henrik

    2009-01-01

    We present the ongoing work on the pathway analysis of a stochastic calculus. Firstly we present a particular stochastic calculus that we have chosen for our modeling - the Interactive Markov Chains calculus, IMC for short. After that we specify a few restrictions that we have introduced into the......We present the ongoing work on the pathway analysis of a stochastic calculus. Firstly we present a particular stochastic calculus that we have chosen for our modeling - the Interactive Markov Chains calculus, IMC for short. After that we specify a few restrictions that we have introduced...

  17. Pathways to School Success

    Science.gov (United States)

    University of Pittsburgh Office of Child Development, 2012

    2012-01-01

    In 2006, the University of Pittsburgh Office of Child Development began implementing a multi-year school readiness project in several area schools. Evidence from both research and the field point to several key elements that foster school readiness and create pathways to school success for all children. This paper presents components of a…

  18. Policies built upon pathways

    NARCIS (Netherlands)

    S. Musterd; Z. Kovács

    2013-01-01

    After the general introductions, the first substantive part of this volume (Part II) provides concise research-based discussions of policies developed in recognition of the important role played by the pathways along which city-regions have travelled. Our research has shown that it is highly importa

  19. Dexter energy transfer pathways.

    Science.gov (United States)

    Skourtis, Spiros S; Liu, Chaoren; Antoniou, Panayiotis; Virshup, Aaron M; Beratan, David N

    2016-07-19

    Energy transfer with an associated spin change of the donor and acceptor, Dexter energy transfer, is critically important in solar energy harvesting assemblies, damage protection schemes of photobiology, and organometallic opto-electronic materials. Dexter transfer between chemically linked donors and acceptors is bridge mediated, presenting an enticing analogy with bridge-mediated electron and hole transfer. However, Dexter coupling pathways must convey both an electron and a hole from donor to acceptor, and this adds considerable richness to the mediation process. We dissect the bridge-mediated Dexter coupling mechanisms and formulate a theory for triplet energy transfer coupling pathways. Virtual donor-acceptor charge-transfer exciton intermediates dominate at shorter distances or higher tunneling energy gaps, whereas virtual intermediates with an electron and a hole both on the bridge (virtual bridge excitons) dominate for longer distances or lower energy gaps. The effects of virtual bridge excitons were neglected in earlier treatments. The two-particle pathway framework developed here shows how Dexter energy-transfer rates depend on donor, bridge, and acceptor energetics, as well as on orbital symmetry and quantum interference among pathways.

  20. Mining biological pathways using WikiPathways web services.

    Directory of Open Access Journals (Sweden)

    Thomas Kelder

    Full Text Available WikiPathways is a platform for creating, updating, and sharing biological pathways [1]. Pathways can be edited and downloaded using the wiki-style website. Here we present a SOAP web service that provides programmatic access to WikiPathways that is complementary to the website. We describe the functionality that this web service offers and discuss several use cases in detail. Exposing WikiPathways through a web service opens up new ways of utilizing pathway information and assisting the community curation process.

  1. Mining biological pathways using WikiPathways web services.

    Science.gov (United States)

    Kelder, Thomas; Pico, Alexander R; Hanspers, Kristina; van Iersel, Martijn P; Evelo, Chris; Conklin, Bruce R

    2009-07-30

    WikiPathways is a platform for creating, updating, and sharing biological pathways [1]. Pathways can be edited and downloaded using the wiki-style website. Here we present a SOAP web service that provides programmatic access to WikiPathways that is complementary to the website. We describe the functionality that this web service offers and discuss several use cases in detail. Exposing WikiPathways through a web service opens up new ways of utilizing pathway information and assisting the community curation process.

  2. Rational design of self-assembly pathways for complex multicomponent structures

    Science.gov (United States)

    Jacobs, William M.; Reinhardt, Aleks; Frenkel, Daan

    2015-01-01

    The field of complex self-assembly is moving toward the design of multiparticle structures consisting of thousands of distinct building blocks. To exploit the potential benefits of structures with such “addressable complexity,” we need to understand the factors that optimize the yield and the kinetics of self-assembly. Here we use a simple theoretical method to explain the key features responsible for the unexpected success of DNA-brick experiments, which are currently the only demonstration of reliable self-assembly with such a large number of components. Simulations confirm that our theory accurately predicts the narrow temperature window in which error-free assembly can occur. Even more strikingly, our theory predicts that correct assembly of the complete structure may require a time-dependent experimental protocol. Furthermore, we predict that low coordination numbers result in nonclassical nucleation behavior, which we find to be essential for achieving optimal nucleation kinetics under mild growth conditions. We also show that, rather surprisingly, the use of heterogeneous bond energies improves the nucleation kinetics and in fact appears to be necessary for assembling certain intricate 3D structures. This observation makes it possible to sculpt nucleation pathways by tuning the distribution of interaction strengths. These insights not only suggest how to improve the design of structures based on DNA bricks, but also point the way toward the creation of a much wider class of chemical or colloidal structures with addressable complexity. PMID:25941388

  3. DMPD: Antiviral innate immunity pathways. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 16474426 Antiviral innate immunity pathways. Seth RB, Sun L, Chen ZJ. Cell Res. 200...6 Feb;16(2):141-7. (.png) (.svg) (.html) (.csml) Show Antiviral innate immunity pathways. PubmedID 16474426 ...Title Antiviral innate immunity pathways. Authors Seth RB, Sun L, Chen ZJ. Publication Cell Res. 2006 Feb;16

  4. Metabolic pathways of trichothecenes.

    Science.gov (United States)

    Wu, Qinghua; Dohnal, Vlastimil; Huang, Lingli; Kuca, Kamil; Yuan, Zonghui

    2010-05-01

    Trichothecenes are a group of mycotoxins mainly produced by the fungi of Fusarium genus. Consumers are particularly concerned over the toxicity and food safety of trichothecenes and their metabolites from food-producing animals. The metabolism of T-2 toxin, deoxynivalenol (DON), nivalenol (NIV), fusarenon-X (FX), diacetoxyscirpenol (DAS), 3-acetyldeoxy-nivalenol (3-aDON), and 15-acetyldeoxynivalenol (15-aDON) in rodents, swine, ruminants, poultry, and humans are reviewed in this article. Metabolic pathways of these mycotoxins are very different. The major metabolic pathways of T-2 toxin in animals are hydrolysis, hydroxylation, de-epoxidation, and conjugation. After being transformed to HT-2 toxin, it undergoes further hydroxylation at C-3' to yield 3'-hydroxy-HT-2 toxin, which is considered as an activation pathway, whereas transformation from T-2 to T-2 tetraol is an inactivation pathway in animals. The typical metabolites of T-2 toxin in animals are HT-2 toxin, T-2 triol, T-2 tetraol, neosolaniol (NEO), 3'-hydroxy-HT-2, and 3'-hydroxy-T-2, whereas HT-2 toxin is the main metabolite in humans. De-epoxidation is an important pathway for detoxification in animals. De-epoxy products, DOM-1, and de-epoxy-NIV are the main metabolites of DON and NIV in most animals, respectively. However, the two metabolites are not found in humans. Deacetyl can occur rapidly on the acetyl derivatives, 3-aDON, 15-aDON, and FX. DAS is metabolized in animals to 15-monoacetoxyscirpenol (15-MAS) via C-4 deacetylation and then transformed to scirpentriol (SCP) via C-15 deacetylation. Finally, the epoxy is lost, yielding de-epoxy-SCP. De-epoxy-15-MAS is also the main metabolite of DAS. 15-MAS is the main metabolite in human skin. The review on the metabolism of trichothecenes will help one to well understand the fate of these toxins' future in animals and humans, as well as provide basic information for the risk assessment of them for food safety.

  5. Identifying dysregulated pathways in cancers from pathway interaction networks

    Directory of Open Access Journals (Sweden)

    Liu Ke-Qin

    2012-06-01

    Full Text Available Abstract Background Cancers, a group of multifactorial complex diseases, are generally caused by mutation of multiple genes or dysregulation of pathways. Identifying biomarkers that can characterize cancers would help to understand and diagnose cancers. Traditional computational methods that detect genes differentially expressed between cancer and normal samples fail to work due to small sample size and independent assumption among genes. On the other hand, genes work in concert to perform their functions. Therefore, it is expected that dysregulated pathways will serve as better biomarkers compared with single genes. Results In this paper, we propose a novel approach to identify dysregulated pathways in cancer based on a pathway interaction network. Our contribution is three-fold. Firstly, we present a new method to construct pathway interaction network based on gene expression, protein-protein interactions and cellular pathways. Secondly, the identification of dysregulated pathways in cancer is treated as a feature selection problem, which is biologically reasonable and easy to interpret. Thirdly, the dysregulated pathways are identified as subnetworks from the pathway interaction networks, where the subnetworks characterize very well the functional dependency or crosstalk between pathways. The benchmarking results on several distinct cancer datasets demonstrate that our method can obtain more reliable and accurate results compared with existing state of the art methods. Further functional analysis and independent literature evidence also confirm that our identified potential pathogenic pathways are biologically reasonable, indicating the effectiveness of our method. Conclusions Dysregulated pathways can serve as better biomarkers compared with single genes. In this work, by utilizing pathway interaction networks and gene expression data, we propose a novel approach that effectively identifies dysregulated pathways, which can not only be used

  6. Update on the Angiotensin converting enzyme 2-Angiotensin (1-7)-MAS receptor axis: fetal programing, sex differences, and intracellular pathways.

    Science.gov (United States)

    Chappell, Mark C; Marshall, Allyson C; Alzayadneh, Ebaa M; Shaltout, Hossam A; Diz, Debra I

    2014-01-09

    The renin-angiotensin-system (RAS) constitutes an important hormonal system in the physiological regulation of blood pressure. Indeed, dysregulation of the RAS may lead to the development of cardiovascular pathologies including kidney injury. Moreover, the blockade of this system by the inhibition of angiotensin converting enzyme (ACE) or antagonism of the angiotensin type 1 receptor (AT1R) constitutes an effective therapeutic regimen. It is now apparent with the identification of multiple components of the RAS that the system is comprised of different angiotensin peptides with diverse biological actions mediated by distinct receptor subtypes. The classic RAS can be defined as the ACE-Ang II-AT1R axis that promotes vasoconstriction, sodium retention, and other mechanisms to maintain blood pressure, as well as increased oxidative stress, fibrosis, cellular growth, and inflammation in pathological conditions. In contrast, the non-classical RAS composed of the ACE2-Ang-(1-7)-Mas receptor axis generally opposes the actions of a stimulated Ang II-AT1R axis through an increase in nitric oxide and prostaglandins and mediates vasodilation, natriuresis, diuresis, and oxidative stress. Thus, a reduced tone of the Ang-(1-7) system may contribute to these pathologies as well. Moreover, the non-classical RAS components may contribute to the effects of therapeutic blockade of the classical system to reduce blood pressure and attenuate various indices of renal injury. The review considers recent studies on the ACE2-Ang-(1-7)-Mas receptor axis regarding the precursor for Ang-(1-7), the intracellular expression and sex differences of this system, as well as an emerging role of the Ang1-(1-7) pathway in fetal programing events and cardiovascular dysfunction.

  7. Update on the Angiotensin Converting Enzyme 2-Angiotensin (1-7-Mas Receptor Axis: Fetal Programming, Sex Differences and Intracellular Pathways

    Directory of Open Access Journals (Sweden)

    Mark C. Chappell

    2014-01-01

    Full Text Available The renin-angiotensin-system (RAS constitutes an important hormonal system in the physiological regulation of blood pressure. Indeed, dysregulation of the RAS may lead to the development of cardiovascular pathologies including kidney injury. Moreover, the blockade of this system by the inhibition of angiotensin converting enzyme (ACE or antagonism of the angiotensin type 1 receptor (AT1R constitutes an effective therapeutic regimen. It is now apparent with the identification of multiple components of the RAS that the system is comprised of different angiotensin peptides with diverse biological actions mediated by distinct receptor subtypes. The classic RAS can be defined as the ACE-Ang II-AT1R axis that promotes vasoconstriction, sodium retention and other mechanisms to maintain blood pressure, as well as increased oxidative stress, fibrosis, cellular growth and inflammation in pathological conditions. In contrast, the non-classical RAS composed of the ACE2-Ang-(1-7-AT7R axis generally opposes the actions of a stimulated Ang II-AT1R axis through an increase in nitric oxide and prostaglandins and mediates vasodilation, natriuresis, diuresis and oxidative stress. Thus, a reduced tone of the Ang-(1-7 system may contribute to these pathologies as well. Moreover, the non-classical RAS components may contribute to the effects of therapeutic blockade of the classical system to reduce blood pressure and attenuate various indices of renal injury. The review considers recent studies on the ACE2-Ang-(1-7-Mas receptor axis regarding the precursor for Ang-(1-7, the intracellular expression and sex differences of this system, as well as an emerging role of the Ang1-(1-7 pathway in fetal programming events and cardiovascular dysfunction.

  8. Update on the Angiotensin Converting Enzyme 2-Angiotensin (1–7)-Mas Receptor Axis: Fetal Programing, Sex Differences, and Intracellular Pathways

    Science.gov (United States)

    Chappell, Mark C.; Marshall, Allyson C.; Alzayadneh, Ebaa M.; Shaltout, Hossam A.; Diz, Debra I.

    2013-01-01

    The renin-angiotensin-system (RAS) constitutes an important hormonal system in the physiological regulation of blood pressure. Indeed, dysregulation of the RAS may lead to the development of cardiovascular pathologies including kidney injury. Moreover, the blockade of this system by the inhibition of angiotensin converting enzyme (ACE) or antagonism of the angiotensin type 1 receptor (AT1R) constitutes an effective therapeutic regimen. It is now apparent with the identification of multiple components of the RAS that the system is comprised of different angiotensin peptides with diverse biological actions mediated by distinct receptor subtypes. The classic RAS can be defined as the ACE-Ang II-AT1R axis that promotes vasoconstriction, sodium retention, and other mechanisms to maintain blood pressure, as well as increased oxidative stress, fibrosis, cellular growth, and inflammation in pathological conditions. In contrast, the non-classical RAS composed of the ACE2-Ang-(1–7)-Mas receptor axis generally opposes the actions of a stimulated Ang II-AT1R axis through an increase in nitric oxide and prostaglandins and mediates vasodilation, natriuresis, diuresis, and oxidative stress. Thus, a reduced tone of the Ang-(1–7) system may contribute to these pathologies as well. Moreover, the non-classical RAS components may contribute to the effects of therapeutic blockade of the classical system to reduce blood pressure and attenuate various indices of renal injury. The review considers recent studies on the ACE2-Ang-(1–7)-Mas receptor axis regarding the precursor for Ang-(1–7), the intracellular expression and sex differences of this system, as well as an emerging role of the Ang1-(1–7) pathway in fetal programing events and cardiovascular dysfunction. PMID:24409169

  9. Cytochromes P450 and Skin Cancer: Role of Local Endocrine Pathways

    Science.gov (United States)

    Slominski, Andrzej T.; Zmijewski, Michal A.; Semak, Igor; Zbytek, Blazej; Pisarchik, Alexander; Li, Wei; Zjawiony, Jordan; Tuckey, Robert C.

    2013-01-01

    Skin is the largest body organ forming a metabolically active barrier between external and internal environments. The metabolic barrier is composed of cytochromes P450 (CYPs) that regulate its homeostasis through activation or inactivation of biologically relevant molecules. In this review we focus our attention on local steroidogenic and secosteroidogenic systems in relation to skin cancer, e.g., prevention, attenuation of tumor progression and therapy. The local steroidogenic system is composed of locally expressed CYPs involved in local production of androgens, estrogens, gluco- and mineralo-corticosteroids from cholesterol (initiated by CYP11A1) or from steroid precursors delivered to the skin, and of their metabolism and/or inactivation. Cutaneous 7-hydroxylases (CYP7A1, CYP7B1 and CYP39) potentially can produce 7-hydroxy/oxy-steroids/sterols with modifying effects on local tumorigenesis. CYP11A1 also transforms 7-dehydrocholesterol (7DHC)→22(OH)7DHC→20,22(OH)2-7DHC→7-dehydropregnenolone, which can be further metabolized to other 5,7-steroidal dienes. These 5,7-dienal intermediates are converted by ultraviolet radiation B (UVB) into secosteroids which show pro-differentiation and anti-cancer properties. Finally, the skin is the site of activation of vitamin D3 through two alternative pathways. The classical one involves sequential hydroxylation at positions 25 and 1 to produce active 1,25(OH)2D3, which is further inactivated through hydroxylation at C24. The novel pathway is initiated by CYP11A1 with predominant production of 20(OH)D3 which is further metabolized to biologically active but non-calcemic D3-hydroxyderivatives. Classical and non-classical (novel) vitamin D analogs show pro-differentiation, anti-proliferative and anticancer properties. In addition, melatonin is metabolized by local CYPs. In conclusion cutaneously expressed CYPs have significant effects on skin physiology and pathology trough regulation of its chemical milieu. PMID:23869782

  10. Mapping Nursing Pathways

    Directory of Open Access Journals (Sweden)

    Melanie Birks

    2015-09-01

    Full Text Available Articulated education pathways between the vocational education training sector and universities provide opportunities for students wishing to progress to higher qualifications. Enrolled nurses seeking to advance their career in nursing can choose to enter baccalaureate degree programs through such alternative entry routes. Awarding of credit for prior studies is dependent on accurate assessment of the existing qualification against that which is sought. This study employed a modified Delphi method to inform the development of an evidence-based, structured approach to mapping the pathway from the nationally consistent training package of the Diploma of Nursing to the diversity of baccalaureate nursing programs across Australia. The findings of this study reflect the practical nature of the role of the enrolled nurse, particularly the greater emphasis placed on direct care activities as opposed to those related to professional development and the generation and use of evidence. These findings provide a valuable summative overview of the relationship between the Diploma of Nursing and the expectations of the registered nurse role.

  11. 关于有限维空间谐振子偶相干态的非经典特性%Numerical Studies on the Nonclassical Properties of Even Coherent States in a Finite-Dimensional Hilbert Space

    Institute of Scientific and Technical Information of China (English)

    邓宏贵; 朱从旭

    2001-01-01

    该文运用数值计算方法研究了有限维希尔伯特空间谐振子偶相干态的非经典特性.研究表明.在有限维情景,偶相干态不仅出现振幅正交分量压缩,而且出现振幅平方压缩和反聚束效应.随着维数s减少,出现两种压缩的区域均缩小且压缩强度减弱;而出现反聚束效应的区域却变大且反聚束程度加强.%The nonclassical properties of even coherent states in a finite-dimensional Hilbert spaces (FDHS) case are studied by numerical method . It is found that, not only quadrature squeezing but also amplitude-squeezing and antibunching effects exist in the states. With the number of dimension reducing, both quadrate squeezing and amplitudesqueezing effects are weakened,but the antibunching effect is Enhanced.

  12. A pathway linking oxidative stress and the Ran GTPase system in progeria.

    Science.gov (United States)

    Datta, Sutirtha; Snow, Chelsi J; Paschal, Bryce M

    2014-04-01

    Maintaining the Ran GTPase at a proper concentration in the nucleus is important for nucleocytoplasmic transport. Previously we found that nuclear levels of Ran are reduced in cells from patients with Hutchinson-Gilford progeria syndrome (HGPS), a disease caused by constitutive attachment of a mutant form of lamin A (termed progerin) to the nuclear membrane. Here we explore the relationship between progerin, the Ran GTPase, and oxidative stress. Stable attachment of progerin to the nuclear membrane disrupts the Ran gradient and results in cytoplasmic localization of Ubc9, a Ran-dependent import cargo. Ran and Ubc9 disruption can be induced reversibly with H2O2. CHO cells preadapted to oxidative stress resist the effects of progerin on Ran and Ubc9. Given that HGPS-patient fibroblasts display elevated ROS, these data suggest that progerin inhibits nuclear transport via oxidative stress. A drug that inhibits pre-lamin A cleavage mimics the effects of progerin by disrupting the Ran gradient, but the effects on Ran are observed before a substantial ROS increase. Moreover, reducing the nuclear concentration of Ran is sufficient to induce ROS irrespective of progerin. We speculate that oxidative stress caused by progerin may occur upstream or downstream of Ran, depending on the cell type and physiological setting.

  13. Non-classical processes in surface hemostasis: mechanisms for the poly-N-acetyl glucosamine-induced alteration of red blood cell morphology and surface prothrombogenicity

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, Thomas H; Smith, Carr J; Scull, Christopher M; Merricks, Elizabeth P; Nichols, Timothy C [Francis Owen Blood Research Laboratory, Department of Pathology and Laboratory Medicine, 125 University Lake Dr., CB 3114, University of North Carolina at Chapel Hill, NC (United States); Valeri, C Robert [Naval Blood Research Laboratory, Inc., Boston, MA (United States); Demcheva, Marina; Vournakis, John N [Marine Polymer Technologies, Inc., Danvers, MA (United States)

    2008-03-01

    It is well established that platelets and the intrinsic plasma coagulation pathway can be activated when blood contacts artificial surfaces. Experiments were performed to assess the effect of hemostatic poly-N-acetyl glucosamine (pGlcNAc) nanofibers on red blood cells. The pGlcNAc nanofibers, isolated from a marine diatom, interact with red blood cells (RBCs) to produce stomatocytes. The stomatocytes could be converted to echinocytes by treatment with echinocytic reagents, as measured by electron microscopy. Electrophoretic and Western blot analysis of RBC surface proteins demonstrated that pGlcNAc fibers were bound to band 3 of the RBC. An important and unique result of the interaction of RBCs with pGlcNAc fibers was the activation of the intrinsic coagulation cascade. This prothrombotic effect was associated with the presentation of phosphatidylserine on the outer layer of the surface membrane of nanofiber bound RBCs. The results demonstrate that RBCs can play a direct and important role in achieving surface hemostasis by accelerating the generation of thrombin, and add to the growing body of evidence that RBCs can strongly interact with hemostatic systems.

  14. Combined treatment with fenretinide and indomethacin induces AIF-mediated, non-classical cell death in human acute T-cell leukemia Jurkat cells

    Energy Technology Data Exchange (ETDEWEB)

    Hojka-Osinska, Anna, E-mail: hojka@immuno.iitd.pan.wroc.pl [Laboratory of Tumor Molecular Immunobiology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, 53-114 Wroclaw (Poland); Ziolo, Ewa, E-mail: ziolo@immuno.iitd.pan.wroc.pl [Laboratory of Tumor Molecular Immunobiology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, 53-114 Wroclaw (Poland); Rapak, Andrzej, E-mail: rapak@immuno.iitd.pan.wroc.pl [Laboratory of Tumor Molecular Immunobiology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, 53-114 Wroclaw (Poland)

    2012-03-16

    Highlights: Black-Right-Pointing-Pointer The combination of fenretinide and indomethacin induces a high level of cell death. Black-Right-Pointing-Pointer Apoptotic pathway is caspase-independent. Black-Right-Pointing-Pointer Jurkat cells undergo AIF-mediated cell death. -- Abstract: Currently used cytotoxic drugs in cancer therapy have a similar mechanism of action and low specificity. Applied simultaneously, they show an additive effect with strong side effects. Clinical trials with the use of different agents in cancer therapy show that the use of these compounds alone is not very effective in fighting cancer. An alternative solution could be to apply a combination of these agents, because their combination has a synergistic effect on some cancer cells. Therefore, in our investigations we examined the effects of a synthetic retinoid-fenretinide when combined with a non-steroidal anti-inflammatory drug-indomethacin on the process of apoptosis in the acute human T-cell leukemia cell line Jurkat. We demonstrate that treatment with the combination of the tested compounds induces the death of cells, that is peculiar and combines features of apoptosis as well as non-apoptotic cell death. In detail we observed, cell membrane permeabilization, phosphatydylserine exposure, no oligonucleosomal DNA fragmentation, no caspase-3 activation, but apoptosis inducing factor (AIF) nuclear translocation. Taken together these results indicate, that Jurkat cells after treatment with a combination of fenretinide and indomethacin undergo AIF-mediated programmed cell death.

  15. Pathways to Global Markets

    DEFF Research Database (Denmark)

    Smith, David E.; Mitry, Darryl J.

    2011-01-01

    For marketing and economic researchers, an important aspect of globalization is the degree to which various consumer behavior dimensions and consumption patterns in different parts of the world are becoming similar, and how multinational companies have identified pathways to global success....... An important case study is McDonald‘s corporation, the world‘s largest fast food restaurant chain. This company has employed divergent marketing and economic strategies in both domestic and the international markets to become a leader in the global marketplace. An overview of the company‘s background......, organizational structures, mission and vision illustrate McDonald‘s strategic focus on its proactive evolution from a small drive-through operation to a global fast-food giant. The strategy is based on its ability to adapt to the cultural differences of the markets that McDonald‘s serves while preserving its...

  16. GPR30, the non-classical membrane G protein related estrogen receptor, is overexpressed in human seminoma and promotes seminoma cell proliferation.

    Directory of Open Access Journals (Sweden)

    Nicolas Chevalier

    Full Text Available BACKGROUND: Testicular germ cell tumours are the most frequent cancer of young men with an increasing incidence all over the world. Pathogenesis and reasons of this increase remain unknown but epidemiological and clinical data have suggested that fetal exposure to environmental endocrine disruptors (EEDs with estrogenic effects, could participate to testicular germ cell carcinogenesis. However, these EEDs (like bisphenol A are often weak ligands for classical nuclear estrogen receptors. Several research groups recently showed that the non classical membrane G-protein coupled estrogen receptor (GPER/GPR30 mediates the effects of estrogens and several xenoestrogens through rapid non genomic activation of signal transduction pathways in various human estrogen dependent cancer cells (breast, ovary, endometrium. The aim of this study was to demonstrate that GPER was overexpressed in testicular tumours and was able to trigger JKT-1 seminoma cell proliferation. RESULTS: We report here for the first time a complete morphological and functional characterization of GPER in normal and malignant human testicular germ cells. In normal adult human testes, GPER was expressed by somatic (Sertoli cells and germ cells (spermatogonia and spermatocytes. GPER was exclusively overexpressed in seminomas, the most frequent testicular germ cell cancer, localized at the cell membrane and triggered a proliferative effect on JKT-1 cells in vitro, which was completely abolished by G15 (a GPER selective antagonist and by siRNA invalidation. CONCLUSION: These results demonstrate that GPER is expressed by human normal adult testicular germ cells, specifically overexpressed in seminoma tumours and able to trigger seminoma cell proliferation in vitro. It should therefore be considered rather than classical ERs when xeno-estrogens or other endocrine disruptors are assessed in testicular germ cell cancers. It may also represent a prognosis marker and/or a therapeutic target for

  17. Non-classical effects of prolactin on the innate immune response of bovine mammary epithelial cells: Implications during Staphylococcus aureus internalization.

    Science.gov (United States)

    Medina-Estrada, Ivan; Alva-Murillo, Nayeli; López-Meza, Joel E; Ochoa-Zarzosa, Alejandra

    2015-12-01

    Staphylococcus aureus has the ability to invade mammary epithelial cells (bMECs) causing mastitis. This event depends primarily on the α5β1 integrin in the host cell. In addition, bMECs are a target for the hormone prolactin (PRL), which can regulate β1 integrin-dependent actions related to differentiation and lactation. Previously, we demonstrated that bovine PRL (bPRL, 5 ng/ml) stimulates S. aureus internalization into bMECs. TLR2 is important during S. aureus infections, but its activation by PRL has not yet been established. The objective of this study was to determine the role of α5β1 integrin and TLR2 during S. aureus internalization into bMECs stimulated with bPRL. We demonstrated that the prolactin-stimulated internalization of S. aureus decreases in response to the blockage of α5β1 integrin (∼ 80%) and TLR2 (∼ 80%). bPRL increases the membrane abundance (MA) of α5β1 integrin (∼ 20%) and induces TLR2 MA (∼ 2-fold). S. aureus reduces the α5β1 integrin MA in bMECs treated with bPRL (∼ 75%) but induces TLR2 MA in bMECs (∼ 3-fold). Bacteria and bPRL did not modify TLR2 MA compared with the hormone alone. S. aureus induces the activation of the transcription factor AP-1, which was inhibited in bMECs treated with bPRL and infected. In general, bPRL induces both pro- and anti-inflammatory responses in bMECs, which are abated in response to bacterial challenge. Interestingly, the canonical Stat-5 transcription factor was not activated in the challenged bMECs and/or treated with bPRL. Taken together, these results support novel functions of prolactin as a modulator of the innate immune response that do not involve the classical prolactin pathway.

  18. GPR30, the Non-Classical Membrane G Protein Related Estrogen Receptor, Is Overexpressed in Human Seminoma and Promotes Seminoma Cell Proliferation

    Science.gov (United States)

    Chevalier, Nicolas; Vega, Aurélie; Bouskine, Adil; Siddeek, Bénazir; Michiels, Jean-François; Chevallier, Daniel; Fénichel, Patrick

    2012-01-01

    Background Testicular germ cell tumours are the most frequent cancer of young men with an increasing incidence all over the world. Pathogenesis and reasons of this increase remain unknown but epidemiological and clinical data have suggested that fetal exposure to environmental endocrine disruptors (EEDs) with estrogenic effects, could participate to testicular germ cell carcinogenesis. However, these EEDs (like bisphenol A) are often weak ligands for classical nuclear estrogen receptors. Several research groups recently showed that the non classical membrane G-protein coupled estrogen receptor (GPER/GPR30) mediates the effects of estrogens and several xenoestrogens through rapid non genomic activation of signal transduction pathways in various human estrogen dependent cancer cells (breast, ovary, endometrium). The aim of this study was to demonstrate that GPER was overexpressed in testicular tumours and was able to trigger JKT-1 seminoma cell proliferation. Results We report here for the first time a complete morphological and functional characterization of GPER in normal and malignant human testicular germ cells. In normal adult human testes, GPER was expressed by somatic (Sertoli cells) and germ cells (spermatogonia and spermatocytes). GPER was exclusively overexpressed in seminomas, the most frequent testicular germ cell cancer, localized at the cell membrane and triggered a proliferative effect on JKT-1 cells in vitro, which was completely abolished by G15 (a GPER selective antagonist) and by siRNA invalidation. Conclusion These results demonstrate that GPER is expressed by human normal adult testicular germ cells, specifically overexpressed in seminoma tumours and able to trigger seminoma cell proliferation in vitro. It should therefore be considered rather than classical ERs when xeno-estrogens or other endocrine disruptors are assessed in testicular germ cell cancers. It may also represent a prognosis marker and/or a therapeutic target for seminomas. PMID

  19. A pathway to spirituality.

    Science.gov (United States)

    Shaw, Jon A

    2005-01-01

    The phenomenology of mystical experiences has been described throughout all the ages and in all religions. All mystical traditions identify some sense of union with the absolute as the ultimate spiritual goal. I assume that the pathway to both theistic and secular spirituality and our readiness to seek a solution in a psychological merger with something beyond the self evolves out of our human experience. Spirituality is one of man's strategies for dealing with the limitations of the life cycle, separation and loss, biological fragility, transience, and non-existence. Spirituality may serve as the affective component to a belief system or myth that is not rooted in scientific evidence but is lived as if it is true. Spirituality may take many forms, but I will suggest that in some instances it may serve as a reparative process in which one creates in the external world, through symbolic form, a nuance or facet of an internalized mental representation which has become lost or is no longer available to the self; or it may represent the continuity of the self-representation after death through a self-object merger. Lastly I will illustrate from the writings of two of our greatest poets, Dante Alighieri and William Wordsworth, how their poetry became interwoven with a profound spirituality. In Dante we will see the elaboration of a religious spirituality, while in the writings of Wordsworth a secular spirituality emerges interwoven with nature and belatedly his identification with "tragic man" as his mythos.

  20. 硫酸盐侵蚀下混凝土的非经典非线性效应变化%The changes of the nonclassical nonlinear effect under erosion of sulfate

    Institute of Scientific and Technical Information of China (English)

    王晓惠; 刘晓宙; 龚秀芬; V. E. Nazarov

    2011-01-01

    混凝土由于受硫酸盐侵蚀和干湿循环作用,内部出现微损伤,性能发生劣化.目前国内外针对结构混凝土硫酸盐侵蚀和干湿循环作用对结构混凝土的损伤失效的研究都集中在力学性能方面,关于损伤和劣化规律特别是无损检测的实验研究较少.混凝土无损检测技术一般采用线性超声方法,用非线性声学方法检测混凝土损伤和劣化规律的研究才刚刚起步.岩石、混凝土等非线性介观弹性固体材料显示出与经典非线性声学不同的非经典非线性现象,包括谐波的滋生、非线性频率偏移、非线性参量的变化等.本文实验研究了受硫酸盐侵蚀和干湿循环作用不同程度的六个水泥砂浆棱柱样品的线性与非线性声学特性,分析了混凝土受硫酸盐侵蚀和干湿循环作用后的损伤程度和劣化规律,探讨了使用非经典非线性相关参数来表征混凝土早期微损伤程度的可能性.%When concrete is under sulfate erosion and the wet and dry cycles, the internal micro-damage and performance degradation occur. Studies on structure concrete that is under sulfate erosion and the wet and dry cycles is not enough, the research at present is focused mainly on the mechanical properties of structure concrete. There are few works on the internal micro-damage and the performance degradation of structural concrete. Concrete nondestructive testing techniques are generally using linear ultrasonic method. The nonlinear acoustic method used to obtain the concrete damaging and deteriorating law has just started. Rock, concrete and other nonlinear mesoscopic elastic solids show the nonclassical nonlinear phenomena, including the amplitude of the odd harmonics higher than that of the even harmonics, nonlinear resonance frequency shift and the change of the nonlinear parameters, which are different from those in classical nonlinear. In this paper, the linear and nonlinear acoustic properties of the six

  1. Controlling the Conformational Energy of a Phenyl Group by Tuning the Strength of a Nonclassical CH···O Hydrogen Bond: The Case of 5-Phenyl-1,3-dioxane.

    Science.gov (United States)

    Bailey, William F; Lambert, Kyle M; Stempel, Zachary D; Wiberg, Kenneth B; Mercado, Brandon Q

    2016-12-16

    Anancomeric 5-phenyl-1,3-dioxanes provide a unique opportunity to study factors that control conformation. Whereas one might expect an axial phenyl group at C(5) of 1,3-dioxane to adopt a conformation similar to that in axial phenylcyclohexane, a series of studies including X-ray crystallography, NOE measurements, and DFT calculations demonstrate that the phenyl prefers to lie over the dioxane ring in order to position an ortho-hydrogen to participate in a stabilizing, nonclassical CH···O hydrogen bond with a ring oxygen of the dioxane. Acid-catalyzed equilibration of a series of anancomeric 2-tert-butyl-5-aryl-1,3-dioxane isomers demonstrates that remote substituents on the phenyl ring affect the conformational energy of a 5-aryl-1,3-dioxane: electron-withdrawing substituents decrease the conformational energy of the aryl group, while electron-donating substituents increase the conformational energy of the group. This effect is correlated in a very linear way to Hammett substituent parameters. In short, the strength of the CH···O hydrogen bond may be tuned in a predictable way in response to the electron-withdrawing or electron-donating ability of substituents positioned remotely on the aryl ring. This effect may be profound: a 3,5-bis-CF3 phenyl group at C(5) in 1,3-dioxane displays a pronounced preference for the axial orientation. The results are relevant to broader conformational issues involving heterocyclic systems bearing aryl substituents.

  2. 不是名著的名著--作家决定论下的《恋恋笔记本》赏析%A Non-Classic Classic--The Appreciation of The Notebook under Writer Determinism Theory

    Institute of Scientific and Technical Information of China (English)

    欧阳乐

    2013-01-01

    There are many ways of interpreting a literary work, and in the context of the merging of different disciplines nowa⁃days, it is undoubtedly feasible to do it within a stylistic perspective. Can The Notebook, representative of American bestselling writer Nicholas Sparks, which has been adapted to a movie, and also a bestseller on the ranking list of New York Times, be called world classic? The main reflection of the Romantic Movement which sprang up in the 18th century on the stylistic theories is writer determinism theory. The popularness as well as some shortcomings of The Notebook can be revealed after careful analysis of it under the frame work of writer determinism theory. It can be concluded that it is indeed a non-classic classic.%  评价一部文学作品有很多种方法,在当今各学科相互融合的背景下,从文体学的角度来阐释无疑是可行的。《恋恋笔记本》,这部被改编成电影、《纽约时报》排行榜上的畅销书,美国畅销小说作家尼古拉斯·斯帕克思的代表作,是否能被称为世界文学名著呢?18世纪兴起的浪漫主义运动在文体学理论上主要反映为作家决定论。通过在作家决定论的理论框架下对其进行分析,可以得出其令人称道之处,同时指出其不足。它的确是一部不是名著的名著。

  3. Structural elucidation of the nonclassical secondary cell wall polysaccharide from Bacillus cereus ATCC 10987. Comparison with the polysaccharides from Bacillus anthracis and B. cereus type strain ATCC 14579 reveals both unique and common structural features.

    Science.gov (United States)

    Leoff, Christine; Choudhury, Biswa; Saile, Elke; Quinn, Conrad P; Carlson, Russell W; Kannenberg, Elmar L

    2008-10-31

    Nonclassical secondary cell wall polysaccharides constitute a major cell wall structure in the Bacillus cereus group of bacteria. The structure of the secondary cell wall polysaccharide from Bacillus cereus ATCC 10987, a strain that is closely related to Bacillus anthracis, was determined. This polysaccharide was released from the cell wall with aqueous hydrogen fluoride (HF) and purified by gel filtration chromatography. The purified polysaccharide, HF-PS, was characterized by glycosyl composition and linkage analyses, mass spectrometry, and one- and two-dimensional NMR analysis. The results showed that the B. cereus ATCC 10987 HF-PS has a repeating oligosaccharide consisting of a -->6)-alpha-GalNAc-(1-->4)-beta-ManNAc-(1-->4)-beta-GlcNAc-(1--> trisaccharide that is substituted with beta-Gal at O3 of the alpha-GalNAc residue and nonstoichiometrically acetylated at O3 of the N-acetylmannosamine (ManNAc) residue. Comparison of this structure with that of the B. anthracis HF-PS and with structural data obtained for the HF-PS from B. cereus type strain ATCC 14579 revealed that each HF-PS had the same general structural theme consisting of three HexNAc and one Hex residues. A common structural feature in the HF-PSs from B. cereus ATCC 10987 and B. anthracis was the presence of a repeating unit consisting of a HexNAc(3) trisaccharide backbone in which two of the three HexNAc residues are GlcNAc and ManNAc and the third can be either GlcNAc or GalNAc. The implications of these results with regard to the possible functions of the HF-PSs are discussed.

  4. Evolution of the TOR Pathway.

    NARCIS (Netherlands)

    Dam, T.J.P. van; Zwartkruis, F.J.; Bos, J.L.; Snel, B.

    2011-01-01

    The TOR kinase is a major regulator of growth in eukaryotes. Many components of the TOR pathway are implicated in cancer and metabolic diseases in humans. Analysis of the evolution of TOR and its pathway may provide fundamental insight into the evolution of growth regulation in eukaryotes and provid

  5. Novel protein regulates ERK pathway

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ The ERK (extracellular signal-regulated kinase) pathway plays a critical role in the vital processes of living cells such as proliferation and differentiation.Recently, CAS scientists in Shanghai have discovered a novel mechanism of spatial regulation on ERK pathway. The result was published in the 4 September issue of the Proceedings of National Academy of Sciences(PNAS).

  6. Autism: Many Genes, Common Pathways?

    OpenAIRE

    Geschwind, Daniel H.

    2008-01-01

    Autism is a heterogeneous neurodevelopmental syndrome with a complex genetic etiology. It is still not clear whether autism comprises a vast collection of different disorders akin to intellectual disability or a few disorders sharing common aberrant pathways. Unifying principles among cases of autism are likely to be at the level of brain circuitry in addition to molecular pathways.

  7. Autism: many genes, common pathways?

    Science.gov (United States)

    Geschwind, Daniel H

    2008-10-31

    Autism is a heterogeneous neurodevelopmental syndrome with a complex genetic etiology. It is still not clear whether autism comprises a vast collection of different disorders akin to intellectual disability or a few disorders sharing common aberrant pathways. Unifying principles among cases of autism are likely to be at the level of brain circuitry in addition to molecular pathways.

  8. Evolution of the TOR Pathway.

    NARCIS (Netherlands)

    Dam, T.J.P. van; Zwartkruis, F.J.; Bos, J.L.; Snel, B.

    2011-01-01

    The TOR kinase is a major regulator of growth in eukaryotes. Many components of the TOR pathway are implicated in cancer and metabolic diseases in humans. Analysis of the evolution of TOR and its pathway may provide fundamental insight into the evolution of growth regulation in eukaryotes and provid

  9. Novel metabolic pathways in Archaea.

    Science.gov (United States)

    Sato, Takaaki; Atomi, Haruyuki

    2011-06-01

    The Archaea harbor many metabolic pathways that differ to previously recognized classical pathways. Glycolysis is carried out by modified versions of the Embden-Meyerhof and Entner-Doudoroff pathways. Thermophilic archaea have recently been found to harbor a bi-functional fructose-1,6-bisphosphate aldolase/phosphatase for gluconeogenesis. A number of novel pentose-degrading pathways have also been recently identified. In terms of anabolic metabolism, a pathway for acetate assimilation, the methylaspartate cycle, and two CO2-fixing pathways, the 3-hydroxypropionate/4-hydroxybutyrate cycle and the dicarboxylate/4-hydroxybutyrate cycle, have been elucidated. As for biosynthetic pathways, recent studies have clarified the enzymes responsible for several steps involved in the biosynthesis of inositol phospholipids, polyamine, coenzyme A, flavin adeninedinucleotide and heme. By examining the presence/absence of homologs of these enzymes on genome sequences, we have found that the majority of these enzymes and pathways are specific to the Archaea. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. Biogenetic Pathways for Marine Terpenoids

    Institute of Scientific and Technical Information of China (English)

    郑其煌; 苏镜娱; 黄起鹏; 王植材; 刘璇; 高碧; 曾陇梅; 郑德炫

    1994-01-01

    A reasonable theoretical elucidation of biogenetic pathways is given for marine ter-penoids——halogenated terpenoids,cernbranolides and tetracyclic tetraterpenoids in marine organisms ac-cording to biogenesis,and the possibility of studying biogenetic pathways by chemical synthesis and molecu-lar probe method is discussed.

  11. KeyPathwayMinerWeb

    DEFF Research Database (Denmark)

    List, Markus; Alcaraz, Nicolas; Dissing-Hansen, Martin;

    2016-01-01

    We present KeyPathwayMinerWeb, the first online platform for de novo pathway enrichment analysis directly in the browser. Given a biological interaction network (e.g. protein-protein interactions) and a series of molecular profiles derived from one or multiple OMICS studies (gene expression...

  12. Refining the quantitative pathway of the Pathways to Mathematics model.

    Science.gov (United States)

    Sowinski, Carla; LeFevre, Jo-Anne; Skwarchuk, Sheri-Lynn; Kamawar, Deepthi; Bisanz, Jeffrey; Smith-Chant, Brenda

    2015-03-01

    In the current study, we adopted the Pathways to Mathematics model of LeFevre et al. (2010). In this model, there are three cognitive domains--labeled as the quantitative, linguistic, and working memory pathways--that make unique contributions to children's mathematical development. We attempted to refine the quantitative pathway by combining children's (N=141 in Grades 2 and 3) subitizing, counting, and symbolic magnitude comparison skills using principal components analysis. The quantitative pathway was examined in relation to dependent numerical measures (backward counting, arithmetic fluency, calculation, and number system knowledge) and a dependent reading measure, while simultaneously accounting for linguistic and working memory skills. Analyses controlled for processing speed, parental education, and gender. We hypothesized that the quantitative, linguistic, and working memory pathways would account for unique variance in the numerical outcomes; this was the case for backward counting and arithmetic fluency. However, only the quantitative and linguistic pathways (not working memory) accounted for unique variance in calculation and number system knowledge. Not surprisingly, only the linguistic pathway accounted for unique variance in the reading measure. These findings suggest that the relative contributions of quantitative, linguistic, and working memory skills vary depending on the specific cognitive task. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Pathways Intern Report

    Science.gov (United States)

    Bell, Evan A.

    2015-01-01

    During my time at NASA, I worked with the Granular Mechanics and Regolith Organization (GMRO), better known as Swamp Works. The goal of the lab is to find ways to utilize resources found after the astronaut or robot has landed on another planet or asteroid. This concept is known as in-situ resource utilization and it is critical to long term missions such as those to Mars. During my time here I worked on the Asteroid and Lava Tube Free Flyer project (ALTFF). A lava tube, such as the one shown in figure 1, is a long tear drop shaped cavern that is produced when molten lava tunnels through the surrounding rock creating large unground pathways. Before mining for resources on Mars or on asteroids, a sampling mission must be done to scout out useful resource deposits. ALTFF's goal is to provide a low cost, autonomous scout robot that can sample the surface and return to the mother ship or lander for further processing of the samples. The vehicle will be looking for water ice in the regolith that can be processed into either potable water, hydrogen and oxygen fuel, or a binder material for 3D printing. By using a low cost craft to sample, there is much less risk to the more expensive mother ship or lander. While my main task was the construction of a simulation environment to test control code in and the construction of the asteroid free flyer prototype, there were other tasks that I performed relating to the ALTFF project.

  14. Protein design for pathway engineering.

    Science.gov (United States)

    Eriksen, Dawn T; Lian, Jiazhang; Zhao, Huimin

    2014-02-01

    Design and construction of biochemical pathways has increased the complexity of biosynthetically-produced compounds when compared to single enzyme biocatalysis. However, the coordination of multiple enzymes can introduce a complicated set of obstacles to overcome in order to achieve a high titer and yield of the desired compound. Metabolic engineering has made great strides in developing tools to optimize the flux through a target pathway, but the inherent characteristics of a particular enzyme within the pathway can still limit the productivity. Thus, judicious protein design is critical for metabolic and pathway engineering. This review will describe various strategies and examples of applying protein design to pathway engineering to optimize the flux through the pathway. The proteins can be engineered for altered substrate specificity/selectivity, increased catalytic activity, reduced mass transfer limitations through specific protein localization, and reduced substrate/product inhibition. Protein engineering can also be expanded to design biosensors to enable high through-put screening and to customize cell signaling networks. These strategies have successfully engineered pathways for significantly increased productivity of the desired product or in the production of novel compounds.

  15. Protein Design for Pathway Engineering

    Science.gov (United States)

    Eriksen, Dawn T.; Lian, Jiazhang; Zhao, Huimin

    2013-01-01

    Design and construction of biochemical pathways has increased the complexity of biosynthetically-produced compounds when compared to single enzyme biocatalysis. However, the coordination of multiple enzymes can introduce a complicated set of obstacles to overcome in order to achieve a high titer and yield of the desired compound. Metabolic engineering has made great strides in developing tools to optimize the flux through a target pathway, but the inherent characteristics of a particular enzyme within the pathway can still limit the productivity. Thus, judicious protein design is critical for metabolic and pathway engineering. This review will describe various strategies and examples of applying protein design to pathway engineering to optimize the flux through the pathway. The proteins can be engineered for altered substrate specificity/selectivity, increased catalytic activity, reduced mass transfer limitations through specific protein localization, and reduced substrate/product inhibition. Protein engineering can also be expanded to design biosensors to enable high through-put screening and to customize cell signaling networks. These strategies have successfully engineered pathways for significantly increased productivity of the desired product or in the production of novel compounds. PMID:23558037

  16. Jasmonate Signal Pathway in Arabidopsis

    Institute of Scientific and Technical Information of China (English)

    Xiao-Yi Shan; Zhi-Long Wang; Daoxin Xie

    2007-01-01

    Jasmonates (JAs), which include jasmonic acid and its cyclopentane derivatives are synthesized from the octadecanoid pathway and widely distributed throughout the plant kingdom. JAs modulate the expression of numerous genes and mediate responses to stress, wounding, insect attack, pathogen infection, and UV damage. They also affect a variety of processes in many plant developmental processes. The JA signal pathway involves two important events: the biosynthesis of JA and the transduction of JA signal. Several important Arabidopsis mutants in jasmonate signal pathway were described in this review.

  17. Neuroinflammation pathways: a general review.

    Science.gov (United States)

    Shabab, Tara; Khanabdali, Ramin; Moghadamtousi, Soheil Zorofchian; Kadir, Habsah Abdul; Mohan, Gokula

    2017-07-01

    Activated microglial cells play an important role in immune and inflammatory responses in central nervous system and neurodegenerative diseases. Many pro-apoptotic pathways are mediated by signaling molecules that are produced during neuroinflammation. In glial cells, NF-κB, a transcription factor, initiates and regulates the expression of several inflammatory processes during inflammation which are attributed to the pathology of the several neurodegenerative diseases. In this review, we discuss the most important neuroinflammatory mediators with their pathways. Attenuating cytokines production and controlling microglial inflammatory response, which are the result of understanding neuroinflammation pathways, are considered therapeutic strategies for treating neurodegenerative diseases with an inflammatory component.

  18. PaxtoolsR: pathway analysis in R using Pathway Commons.

    Science.gov (United States)

    Luna, Augustin; Babur, Özgün; Aksoy, Bülent Arman; Demir, Emek; Sander, Chris

    2016-04-15

    PaxtoolsR package enables access to pathway data represented in the BioPAX format and made available through the Pathway Commons webservice for users of the R language to aid in advanced pathway analyses. Features include the extraction, merging and validation of pathway data represented in the BioPAX format. This package also provides novel pathway datasets and advanced querying features for R users through the Pathway Commons webservice allowing users to query, extract and retrieve data and integrate these data with local BioPAX datasets. The PaxtoolsR package is compatible with versions of R 3.1.1 (and higher) on Windows, Mac OS X and Linux using Bioconductor 3.0 and is available through the Bioconductor R package repository along with source code and a tutorial vignette describing common tasks, such as data visualization and gene set enrichment analysis. Source code and documentation are at http://www.bioconductor.org/packages/paxtoolsr This plugin is free, open-source and licensed under the LGPL-3. paxtools@cbio.mskcc.org or lunaa@cbio.mskcc.org. © The Author 2015. Published by Oxford University Press.

  19. Noise Trauma Induced Plastic Changes in Brain Regions outside the Classical Auditory Pathway

    Science.gov (United States)

    Chen, Guang-Di; Sheppard, Adam; Salvi, Richard

    2017-01-01

    The effects of intense noise exposure on the classical auditory pathway have been extensively investigated; however, little is known about the effects of noise-induced hearing loss on non-classical auditory areas in the brain such as the lateral amygdala (LA) and striatum (Str). To address this issue, we compared the noise-induced changes in spontaneous and tone-evoked responses from multiunit clusters (MUC) in the LA and Str with those seen in auditory cortex (AC). High-frequency octave band noise (10–20 kHz) and narrow band noise (16–20 kHz) induced permanent thresho ld shifts (PTS) at high-frequencies within and above the noise band but not at low frequencies. While the noise trauma significantly elevated spontaneous discharge rate (SR) in the AC, SRs in the LA and Str were only slightly increased across all frequencies. The high-frequency noise trauma affected tone-evoked firing rates in frequency and time dependent manner and the changes appeared to be related to severity of noise trauma. In the LA, tone-evoked firing rates were reduced at the high-frequencies (trauma area) whereas firing rates were enhanced at the low-frequencies or at the edge-frequency dependent on severity of hearing loss at the high frequencies. The firing rate temporal profile changed from a broad plateau to one sharp, delayed peak. In the AC, tone-evoked firing rates were depressed at high frequencies and enhanced at the low frequencies while the firing rate temporal profiles became substantially broader. In contrast, firing rates in the Str were generally decreased and firing rate temporal profiles become more phasic and less prolonged. The altered firing rate and pattern at low frequencies induced by high frequency hearing loss could have perceptual consequences. The tone-evoked hyperactivity in low-frequency MUC could manifest as hyperacusis whereas the discharge pattern changes could affect temporal resolution and integration. PMID:26701290

  20. Multiple pathways regulate shoot branching

    Directory of Open Access Journals (Sweden)

    Catherine eRameau

    2015-01-01

    Full Text Available Shoot branching patterns result from the spatio-temporal regulation of axillary bud outgrowth. Numerous endogenous, developmental and environmental factors are integrated at the bud and plant levels to determine numbers of growing shoots. Multiple pathways that converge to common integrators are most probably involved. We propose several pathways involving not only the classical hormones auxin, cytokinins and strigolactones, but also other signals with a strong influence on shoot branching such as gibberellins, sugars or molecular actors of plant phase transition. We also deal with recent findings about the molecular mechanisms and the pathway involved in the response to shade as an example of an environmental signal controlling branching. We propose the TCP transcription factor TB1/BRC1 and the polar auxin transport stream in the stem as possible integrators of these pathways. We finally discuss how modeling can help to represent this highly dynamic system by articulating knowledges and hypothesis and calculating the phenotype properties they imply.

  1. The Oxylipin Pathway in Arabidopsis

    OpenAIRE

    Creelman, Robert A.; Mulpuri, Rao

    2002-01-01

    Oxylipins are acyclic or cyclic oxidation products derived from the catabolism of fatty acids which regulate many defense and developmental pathways in plants. The dramatic increase in the volume of publications and reviews on these compounds since 1997 documents the increasing interest in this compound and its role in plants. Research on this topic has solidified our understanding of the chemistry and biosynthetic pathways for oxylipin production. However, more information is still needed on...

  2. Session on computation in biological pathways

    Energy Technology Data Exchange (ETDEWEB)

    Karp, P.D. [SRI International, Menlo Park, CA (United States); Riley, M. [Marine Biological Lab., Woods Hole, MA (United States)

    1996-12-31

    The papers in this session focus on the development of pathway databases and computational tools for pathway analysis. The discussion involves existing databases of sequenced genomes, as well as techniques for studying regulatory pathways.

  3. 3例非典型异戊酸尿症患儿临床及基因型研究%Clinical and genetic features of three patients with non-classical isovaleric aciduria

    Institute of Scientific and Technical Information of China (English)

    李溪远; 秦亚萍; 杨艳玲; 华瑛; 丁圆; 吴桐菲; 宋金青; 刘玉鹏; 王峤; 张尧; 李梦秋

    2014-01-01

    Objective To explore the clinical, therapeutic and genetic features of IVD gene in late-onset non-classical isovaleric aciduria. Methods One boy and two girls presented with intractable vomiting were admitted. Urine organic acids and blood acylcarnitines proifles were analyzed. Isovaleric aciduria was diagnosed and conifrmed by IVD gene analysis. The patients were treated with leucine-restricted diet and the supplements of L-carnitine and glycine. Results Three patients had recurrent vomiting, drowsiness, odor of sweaty feet and metabolic acidosis from the age of 1 to 2 years. All of them had normal intelligence and leukopenia. One had oligocythemia. The blood isovalerylcarnitines (4.6 to 8.2μmol/L) and urine isovalerylglycines (36.1 to 1783.56 mmol/mmol creatinine) were elevated. Six mutations were found in their IVD gene. Four mutations (c.157C>T, c.214G>A, c.1183C>G and c.1208A>G) were reported. Two (c.1039G>A and c.1076A>G) were novel. The patients completely recovered after treatment with protein-restricted diet and the supplements of L-carnitine and glycine. Currently, they were aged 19 months to 14 years with normal physical and psychomotor development. Conclusions The clinical features of late-onset non-classical isovaleric aciduria are complex. It is onset in infants and young children and characteristic of recurrent vomiting and metabolic acidosis, which can be diagnosed by the blood acylcarnitine spectrum, urine organic acid analysis, and conifrmed by genetic analysis. L-carnitine supplement and diet intervention has signiifcant effects.%目的:探讨迟发型非典型异戊酸尿症患儿的临床、治疗及IVD基因突变特点。方法3例非典型异戊酸尿症患儿,经尿液有机酸、血液酯酰肉碱谱分析发现异戊酸尿症,并经IVD基因突变检测确诊。患儿给予左卡尼汀、甘氨酸补充治疗及限亮氨酸饮食干预并进行随访。结果3例患儿于1~2岁间发病,有不明原因呕吐、嗜睡,伴汗

  4. LXR signaling pathways and atherosclerosis

    Science.gov (United States)

    Calkin, Anna; Tontonoz, Peter

    2010-01-01

    First discovered as orphan receptors, liver X receptors (LXRs) were subsequently identified as the nuclear receptor target of the cholesterol metabolites, oxysterols.1 There are 2 LXR receptors encoded by distinct genes: LXRα is most highly expressed in the liver, adipose, kidney, adrenal tissues and macrophages, and LXRβ is ubiquitously expressed. Despite differential tissue distribution, these isoforms have 78% homology in their ligand-binding domain and appear to respond to the same endogenous ligands. Work over the past 10 years has shown that the LXR pathway regulates lipid metabolism and inflammation via both the induction and repression of target genes. Given the importance of cholesterol regulation and inflammation in the development of cardiovascular disease, it is not surprising that activation of the LXR pathway attenuates various mechanisms underlying atherosclerotic plaque development.2 In this minireview we will discuss the impact of the LXR pathway on both cholesterol metabolism and atherosclerosis. PMID:20631351

  5. Applications Of Nonclassical Geometry To String Theory

    CERN Document Server

    Zunger, Y

    2003-01-01

    String theory is built on a foundation of geometry. This thesis examines several applications of geometry beyond the classical Riemannian geometry of curved surfaces. The first part considers the use of extended spaces with internal dimensions to each point (“twistors”) to probe systems with a great deal of symmetry but complicated dynamics. These systems are of critical interest in understanding holographic phenomena in string theory and the origins of entropy. We develop a twistor formulation of coset spaces and use this to write simplified actions for particles and strings on anti-de Sitter space, which are easier to quantize than the ordinary (highly nonlinear) actions. In the second part, we consider two aspects of noncommutative geometry, a generalization of ordinary geometry where points are “fuzzed out” and functions of space become noncommuting operators. We first examine strings with one endpoint on a D-brane in a background magnetic field. (Strings with both ...

  6. A survey of non-classical polyandry.

    Science.gov (United States)

    Starkweather, Katherine E; Hames, Raymond

    2012-06-01

    We have identified a sample of 53 societies outside of the classical Himalayan and Marquesean area that permit polyandrous unions. Our goal is to broadly describe the demographic, social, marital, and economic characteristics of these societies and to evaluate some hypotheses of the causes of polyandry. We demonstrate that although polyandry is rare it is not as rare as commonly believed, is found worldwide, and is most common in egalitarian societies. We also argue that polyandry likely existed during early human history and should be examined from an evolutionary perspective. Our analysis reveals that it may be a predictable response to a high operational sex ratio favoring males and may also be a response to high rates of male mortality and, possibly, male absenteeism. Other factors may contribute, but our within-polyandry sample limits analysis.

  7. Nonclassical measurements errors in nonlinear models

    DEFF Research Database (Denmark)

    Madsen, Edith; Mulalic, Ismir

    Discrete choice models and in particular logit type models play an important role in understanding and quantifying individual or household behavior in relation to transport demand. An example is the choice of travel mode for a given trip under the budget and time restrictions that the individuals...... estimates of the income effect it is of interest to investigate the magnitude of the estimation bias and if possible use estimation techniques that take the measurement error problem into account. We use data from the Danish National Travel Survey (NTS) and merge it with administrative register data...... of a households face. In this case an important policy parameter is the effect of income (reflecting the household budget) on the choice of travel mode. This paper deals with the consequences of measurement error in income (an explanatory variable) in discrete choice models. Since it is likely to give misleading...

  8. Organometallic chemistry in non-classical environments.

    Science.gov (United States)

    Dyson, Paul J

    2011-01-01

    A summary of our on-going research on organometallic chemistry is provided with an emphasis on the function, reactivity and mechanisms of organometallic compounds in water, ionic liquids and in living systems. The role of organometallic compounds in both catalysis and medicinal chemistry are briefly described.

  9. Tissue factor pathway inhibitor endocytosis.

    Science.gov (United States)

    Schwartz, A L; Broze, G J

    1997-10-01

    Tissue factor pathway inhibitor (TFPI), a 42 kD protein, provides the physiological inhibition of tissue factor initiated coagulation by inhibition of both factor Xa and factor VIIa/tissue factor. In plasma, most TFPI is lipoprotein bound with an additional "releasable" pool bound to the endothelial cell surface. TFPI clearance is via receptor mediated endocytosis into liver. Heparin sulfate proteoglycans and LRP (low density lipoprotein receptor-related protein), an extremely large (∼600 kD) cell surface protein, primarily mediate this clearance, although additional TFPI binding sites and endocytosis pathways exist. (Trends Cardiovasc Med 1997; 7:234-239). © 1997, Elsevier Science Inc.

  10. [Pathways of flowering regulation in plants].

    Science.gov (United States)

    Liu, Yongping; Yang, Jing; Yang, Mingfeng

    2015-11-01

    Flowering, the floral transition from vegetative growth to reproductive growth, is induced by diverse endogenous and exogenous cues, such as photoperiod, temperature, hormones and age. Precise flowering time is critical to plant growth and evolution of species. The numerous renewal molecular and genetic results have revealed five flowering time pathways, including classical photoperiod pathway, vernalization pathway, autonomous pathway, gibberellins (GA) pathway and newly identified age pathway. These pathways take on relatively independent role, and involve extensive crosstalks and feedback loops. This review describes the complicated regulatory network of this floral transition to understand the molecular mechanism of flowering and provide references for further research in more plants.

  11. Auditory pathways: anatomy and physiology.

    Science.gov (United States)

    Pickles, James O

    2015-01-01

    This chapter outlines the anatomy and physiology of the auditory pathways. After a brief analysis of the external, middle ears, and cochlea, the responses of auditory nerve fibers are described. The central nervous system is analyzed in more detail. A scheme is provided to help understand the complex and multiple auditory pathways running through the brainstem. The multiple pathways are based on the need to preserve accurate timing while extracting complex spectral patterns in the auditory input. The auditory nerve fibers branch to give two pathways, a ventral sound-localizing stream, and a dorsal mainly pattern recognition stream, which innervate the different divisions of the cochlear nucleus. The outputs of the two streams, with their two types of analysis, are progressively combined in the inferior colliculus and onwards, to produce the representation of what can be called the "auditory objects" in the external world. The progressive extraction of critical features in the auditory stimulus in the different levels of the central auditory system, from cochlear nucleus to auditory cortex, is described. In addition, the auditory centrifugal system, running from cortex in multiple stages to the organ of Corti of the cochlea, is described.

  12. KeyPathwayMinerWeb

    DEFF Research Database (Denmark)

    List, Markus; Alcaraz, Nicolas; Dissing-Hansen, Martin

    2016-01-01

    such as data integration, input of background knowledge, batch runs for parameter optimization and visualization of extracted pathways. In addition to an intuitive web interface, we also implemented a RESTful API that now enables other online developers to integrate network enrichment as a web service...

  13. The lectin pathway of complement

    DEFF Research Database (Denmark)

    Ballegaard, Vibe Cecilie Diederich; Haugaard, Anna Karen; Garred, P

    2014-01-01

    The pattern recognition molecules of the lectin complement pathway are important components of the innate immune system with known functions in host-virus interactions. This paper summarizes current knowledge of how these intriguing molecules, including mannose-binding lectin (MBL), Ficolin-1, -2...

  14. Loco signaling pathway in longevity.

    Science.gov (United States)

    Lin, Yuh-Ru; Parikh, Hardik; Park, Yongkyu

    2011-05-01

    Despite the various roles of regulator of G protein signaling (RGS) protein in the G protein signaling pathway that have been defined, the function of RGS has not been characterized in longevity signaling pathways. We found that reduced expression of Loco, a Drosophila RGS protein, resulted in a longer lifespan of flies with stronger resistance to stress, higher MnSOD activity and increased fat content. In contrast, overexpression of the loco gene shortened the fly lifespan significantly, lowered stress resistance and reduced fat content, also indicating that the RGS domain containing GTPase-activating protein (GAP) activity is related to the regulation of longevity. Interestingly, expressional changes of yeast RGS2 and rat RGS14, homologs to the fly Loco, also affected oxidative stress resistance and longevity in the respective species. It is known that Loco inactivates inhibitory Gαi•GTP protein to reduce activity of adenylate cyclase (AC) and RGS14 interacts with activated H-Ras and Raf-1 kinases, which subsequently inhibits ERK phosphorylation. We propose that Loco/RGS14 protein may regulate stress resistance and longevity as an activator in AC-cAMP-PKA pathway and/or as a molecular scaffold that sequesters active Ras and Raf from Ras•GTP-Raf-MEK-ERK signaling pathway. Consistently, our data showed that downregulation of Loco significantly diminishes cAMP amounts and increases p-ERK levels with higher resistance to the oxidative stress.

  15. Solvents and vapor intrusion pathways.

    Science.gov (United States)

    Phillips, Scott D; Krieger, Gary R; Palmer, Robert B; Waksman, Javier C

    2004-08-01

    Vapor intrusion must be recognized appropriately as a separate pathway of contamination. Although many issues resemble those of other forms of contamination (particularly its entryway, which is similar to that of radon seepage), vapor intrusion stands apart as a unique risk requiring case-specific action. This article addresses these issues and the current understanding of the most appropriate and successful remedial actions.

  16. Critical nodes in signalling pathways

    DEFF Research Database (Denmark)

    Taniguchi, Cullen M; Emanuelli, Brice; Kahn, C Ronald

    2006-01-01

    Physiologically important cell-signalling networks are complex, and contain several points of regulation, signal divergence and crosstalk with other signalling cascades. Here, we use the concept of 'critical nodes' to define the important junctions in these pathways and illustrate their unique role...

  17. Reverse Engineering Adverse Outcome Pathways

    Energy Technology Data Exchange (ETDEWEB)

    Perkins, Edward; Chipman, J.K.; Edwards, Stephen; Habib, Tanwir; Falciani, Francesco; Taylor, Ronald C.; Van Aggelen, Graham; Vulpe, Chris; Antczak, Philipp; Loguinov, Alexandre

    2011-01-30

    The toxicological effects of many stressors are mediated through unknown, or poorly characterized, mechanisms of action. We describe the application of reverse engineering complex interaction networks from high dimensional omics data (gene, protein, metabolic, signaling) to characterize adverse outcome pathways (AOPs) for chemicals that disrupt the hypothalamus-pituitary-gonadal endocrine axis in fathead minnows. Gene expression changes in fathead minnow ovaries in response to 7 different chemicals, over different times, doses, and in vivo versus in vitro conditions were captured in a large data set of 868 arrays. We examined potential AOPs of the antiandrogen flutamide using two mutual information theory methods, ARACNE and CLR to infer gene regulatory networks and potential adverse outcome pathways. Representative networks from these studies were used to predict a network path from stressor to adverse outcome as a candidate AOP. The relationship of individual chemicals to an adverse outcome can be determined by following perturbations through the network in response to chemical treatment leading to the nodes associated with the adverse outcome. Identification of candidate pathways allows for formation of testable hypotheses about key biologic processes, biomarkers or alternative endpoints, which could be used to monitor an adverse outcome pathway. Finally, we identify the unique challenges facing the application of this approach in ecotoxicology, and attempt to provide a road map for the utilization of these tools. Key Words: mechanism of action, toxicology, microarray, network inference

  18. The Phenylpropanoid Pathway in Arabidopsis

    Science.gov (United States)

    Fraser, Christopher M.; Chapple, Clint

    2011-01-01

    The phenylpropanoid pathway serves as a rich source of metabolites in plants, being required for the biosynthesis of lignin, and serving as a starting point for the production of many other important compounds, such as the flavonoids, coumarins, and lignans. In spite of the fact that the phenylpropanoids and their derivatives are sometimes classified as secondary metabolites, their relevance to plant survival has been made clear via the study of Arabidopsis and other plant species. As a model system, Arabidopsis has helped to elucidate many details of the phenylpropanoid pathway, its enzymes and intermediates, and the interconnectedness of the pathway with plant metabolism as a whole. These advances in our understanding have been made possible in large part by the relative ease with which mutations can be generated, identified, and studied in Arabidopsis. Herein, we provide an overview of the research progress that has been made in recent years, emphasizing both the genes (and gene families) associated with the phenylpropanoid pathway in Arabidopsis, and the end products that have contributed to the identification of many mutants deficient in the phenylpropanoid metabolism: the sinapate esters. PMID:22303276

  19. The oxylipin pathway in Arabidopsis.

    Science.gov (United States)

    Creelman, Robert A; Mulpuri, Rao

    2002-01-01

    Oxylipins are acyclic or cyclic oxidation products derived from the catabolism of fatty acids which regulate many defense and developmental pathways in plants. The dramatic increase in the volume of publications and reviews on these compounds since 1997 documents the increasing interest in this compound and its role in plants. Research on this topic has solidified our understanding of the chemistry and biosynthetic pathways for oxylipin production. However, more information is still needed on how free fatty acids are produced and the role of beta-oxidation in the biosynthetic pathway for oxylipins. It is also becoming apparent that oxylipin content and composition changes during growth and development and during pathogen or insect attack. Oxylipins such as jasmonic acid (JA) or 12-oxo-phytodienoic acid modulate the expression of numerous genes and influence specific aspects of plant growth, development and responses to abiotic and biotic stresses. Although oxylipins are believed to act alone, several examples were presented to illustrate that JA-induced responses are modulated by the type and the nature of crosstalk with other signaling molecules such as ethylene and salicylic acid. How oxylipins cause changes in gene expression and instigate a physiological response is becoming understood with the isolation of mutations in both positive and negative regulators in the jasmonate signaling pathway and the use of cDNA microarrays.

  20. Two-Electron Transfer Pathways.

    Science.gov (United States)

    Lin, Jiaxing; Balamurugan, D; Zhang, Peng; Skourtis, Spiros S; Beratan, David N

    2015-06-18

    The frontiers of electron-transfer chemistry demand that we develop theoretical frameworks to describe the delivery of multiple electrons, atoms, and ions in molecular systems. When electrons move over long distances through high barriers, where the probability for thermal population of oxidized or reduced bridge-localized states is very small, the electrons will tunnel from the donor (D) to acceptor (A), facilitated by bridge-mediated superexchange interactions. If the stable donor and acceptor redox states on D and A differ by two electrons, it is possible that the electrons will propagate coherently from D to A. While structure-function relations for single-electron superexchange in molecules are well established, strategies to manipulate the coherent flow of multiple electrons are largely unknown. In contrast to one-electron superexchange, two-electron superexchange involves both one- and two-electron virtual intermediate states, the number of virtual intermediates increases very rapidly with system size, and multiple classes of pathways interfere with one another. In the study described here, we developed simple superexchange models for two-electron transfer. We explored how the bridge structure and energetics influence multielectron superexchange, and we compared two-electron superexchange interactions to single-electron superexchange. Multielectron superexchange introduces interference between singly and doubly oxidized (or reduced) bridge virtual states, so that even simple linear donor-bridge-acceptor systems have pathway topologies that resemble those seen for one-electron superexchange through bridges with multiple parallel pathways. The simple model systems studied here exhibit a richness that is amenable to experimental exploration by manipulating the multiple pathways, pathway crosstalk, and changes in the number of donor and acceptor species. The features that emerge from these studies may assist in developing new strategies to deliver multiple

  1. Forma no clásica de hiperplasia adrenal congénita en la niñez y adolescencia Non-classic way of congenital adrenal hyperplasia in childhood and adolescence

    Directory of Open Access Journals (Sweden)

    Francisco Carvajal Martínez

    2010-04-01

    Full Text Available INTRODUCCIÓN: la hiperplasia adrenal congénita es un trastorno hereditario de la esteroidogénesis suprarrenal, trasmitido por mutaciones genéticas con carácter autosómico recesivo, las cuales afectan las enzimas que intervienen en la biosíntesis del cortisol. La causa la constituye en 90 a 95 % de los casos la deficiencia de la enzima 21 hidroxilasa. OBJETIVO: exponer la experiencia de los autores de este trabajo en la forma no clásica de esta enfermedad. MÉTODOS: se realizó la caracterización de 7 pacientes diagnosticados en la sala de endocrinología pediátrica del Instituto Nacional de Endocrinología, ubicada en el Hospital Pediátrico del Cerro, durante el período 1998-2008. Todos los pacientes pertenecían al sexo femenino. RESULTADOS: los síntomas se iniciaron a una edad promedio de 8,8 años y más de la mitad de los casos presentaron pubarquia precoz. La menarquia se produjo a una edad media de 10,7 años. Se logró el diagnóstico bioquímico al obtenerse valores elevados de 17 hidroxiprogesterona (en condiciones basales. Se emplearon distintas modalidades de tratamiento según la edad de cada paciente y los síntomas predominantes en cada caso. CONCLUSIONES: se corroboró la mayor frecuencia de diagnóstico de esta enfermedad en el sexo femenino, así como la importancia del estudio y el seguimiento ante un paciente con pubarquia precoz.INTRODUCTION: the congenital adrenal hyperplasia is an inherited disorder of suprarenal esteroidogenesis, transmitted by genetic mutations with a autosomal recessive character affecting the enzymes intervening in cortisol biosynthesis. In the 90 to 95% of cases, the cause is a deficiency of Hydroxylase enzyme 21. OBJECTIVE: to show the current paper authors' experience in the non-classic way of this entity. METHODS: we made a characterization of 7 female patients diagnosed in the Children Endocrinology Ward of the National Institute of Endocrinology located in the Children Hospital, Cerro

  2. DMPD: Pathways connecting inflammation and cancer. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18325755 Pathways connecting inflammation and cancer. Allavena P, Garlanda C, Borre...) (.csml) Show Pathways connecting inflammation and cancer. PubmedID 18325755 Title Pathways connecting infl

  3. Hydrogen sulfide in signaling pathways.

    Science.gov (United States)

    Olas, Beata

    2015-01-15

    For a long time hydrogen sulfide (H₂S) was considered a toxic compound, but recently H₂S (at low concentrations) has been found to play an important function in physiological processes. Hydrogen sulfide, like other well-known compounds - nitric oxide (NO) and carbon monoxide (CO) is a gaseous intracellular signal transducer. It regulates the cell cycle, apoptosis and the oxidative stress. Moreover, its functions include neuromodulation, regulation of cardiovascular system and inflammation. In this review, I focus on the metabolism of hydrogen sulfide (including enzymatic pathways of H₂S synthesis from l- and d-cysteine) and its signaling pathways in the cardiovascular system and the nervous system. I also describe how hydrogen sulfide may be used as therapeutic agent, i.e. in the cardiovascular diseases.

  4. Identification of Metabolic Pathway Systems

    Directory of Open Access Journals (Sweden)

    Sepideh eDolatshahi

    2016-02-01

    Full Text Available The estimation of parameters in even moderately large biological systems is a significant challenge. This challenge is greatly exacerbated if the mathematical formats of appropriate process descriptions are unknown. To address this challenge, the method of dynamic flux estimation (DFE was proposed for the analysis of metabolic time series data. Under ideal conditions, the first phase of DFE yields numerical representations of all fluxes within a metabolic pathway system, either as values at each time point or as plots against their substrates and modulators. However, this numerical result does not reveal the mathematical format of each flux. Thus, the second phase of DFE selects functional formats that are consistent with the numerical trends obtained from the first phase. While greatly facilitating metabolic data analysis, DFE is only directly applicable if the pathway system contains as many dependent variables as fluxes. Because most actual systems contain more fluxes than metabolite pools, this requirement is seldom satisfied. Auxiliary methods have been proposed to alleviate this issue, but they are not general. Here we propose strategies that extend DFE toward general, slightly underdetermined pathway systems.

  5. Dual pathways to prospective remembering

    Science.gov (United States)

    McDaniel, Mark A.; Umanath, Sharda; Einstein, Gilles O.; Waldum, Emily R.

    2015-01-01

    According to the multiprocess framework (McDaniel and Einstein, 2000), the cognitive system can support prospective memory (PM) retrieval through two general pathways. One pathway depends on top–down attentional control processes that maintain activation of the intention and/or monitor the environment for the triggering or target cues that indicate that the intention should be executed. A second pathway depends on (bottom–up) spontaneous retrieval processes, processes that are often triggered by a PM target cue; critically, spontaneous retrieval is assumed not to require monitoring or active maintenance of the intention. Given demand characteristics associated with experimental settings, however, participants are often inclined to monitor, thereby potentially masking discovery of bottom–up spontaneous retrieval processes. In this article, we discuss parameters of laboratory PM paradigms to discourage monitoring and review recent behavioral evidence from such paradigms that implicate spontaneous retrieval in PM. We then re-examine the neuro-imaging evidence from the lens of the multiprocess framework and suggest some critical modifications to existing neuro-cognitive interpretations of the neuro-imaging results. These modifications illuminate possible directions and refinements for further neuro-imaging investigations of PM. PMID:26236213

  6. Dual Pathways to Prospective Remembering

    Directory of Open Access Journals (Sweden)

    Mark A Mcdaniel

    2015-07-01

    Full Text Available According to the multiprocess framework (McDaniel & Einstein, 2000, the cognitive system can support prospective memory (PM retrieval through two general pathways. One pathway depends on top-down attentional control processes that maintain activation of the intention and/or monitor the environment for the triggering or target cues that indicate that the intention should be executed. A second pathway depends on (bottom-up spontaneous retrieval processes, processes that are often triggered by a PM target cue; critically spontaneous retrieval is assumed to not require monitoring or active maintenance of the intention. Given demand characteristics associated with experimental settings, however, participants are often inclined to monitor, thereby potentially masking discovery of bottom-up spontaneous retrieval processes. In this article, we discuss parameters of laboratory PM paradigms to discourage monitoring and review recent behavioral evidence from such paradigms that implicate spontaneous retrieval in PM. We then re-examine the neuro-imaging evidence from the lens of the multiprocess framework and suggest some critical modifications to existing neuro-cognitive interpretations of the neuro-imaging results. These modifications illuminate possible directions and refinements for further neuro-imaging investigations of PM.

  7. Imbalanced kynurenine pathway in schizophrenia.

    Science.gov (United States)

    Kegel, Magdalena E; Bhat, Maria; Skogh, Elisabeth; Samuelsson, Martin; Lundberg, Kristina; Dahl, Marja-Liisa; Sellgren, Carl; Schwieler, Lilly; Engberg, Göran; Schuppe-Koistinen, Ina; Erhardt, Sophie

    2014-01-01

    Several studies suggest a role for kynurenic acid (KYNA) in the pathophysiology of schizophrenia. It has been proposed that increased brain KYNA levels in schizophrenia result from a pathological shift in the kynurenine pathway toward enhanced KYNA formation, away from the other branch of the pathway leading to quinolinic acid (QUIN). Here we investigate the levels of QUIN in cerebrospinal fluid (CSF) of patients with schizophrenia and healthy controls, and relate those to CSF levels of KYNA and other kynurenine metabolites from the same individuals. CSF QUIN levels from stable outpatients treated with olanzapine (n = 22) and those of controls (n = 26) were analyzed using liquid chromatography-mass spectrometry. No difference in CSF QUIN levels between patients and controls was observed (20.6 ± 1.5 nM vs. 18.2 ± 1.1 nM, P = 0.36). CSF QUIN was positively correlated to CSF kynurenine and CSF KYNA in patients but not in controls. The CSF QUIN/KYNA ratio was lower in patients than in controls (P = 0.027). In summary, the present study offers support for an over-activated and imbalanced kynurenine pathway, favoring the production of KYNA over QUIN in patients with schizophrenia.

  8. Pathways to Shape the Bioeconomy

    Directory of Open Access Journals (Sweden)

    Carmen Priefer

    2017-02-01

    Full Text Available In view of the increasing depletion of fossil fuel resources, the concept “bioeconomy” aims at the gradual replacement of fossil fuels by renewable feedstock. Seen as a comprehensive societal transition, the bioeconomy is a complex field that includes a variety of sectors, actors, and interests and is related to far-reaching changes in today’s production systems. While the objectives pursued—such as reducing dependence on fossil fuels, mitigating climate change, ensuring global food security, and increasing the industrial use of biogenic resources—are not generally contentious, there is fierce controversy over the possible pathways for achieving these objectives. Based on a thorough literature review, the article identifies major lines of conflict in the current discourse. Criticism of the prevalent concept refers mainly to the strong focus on technology, the lack of consideration given to alternative implementation pathways, the insufficient differentiation of underlying sustainability requirements, and the inadequate participation of societal stakeholders. Since today it cannot be predicted which pathway will be the most expedient—the one already being taken or one of the others proposed—this paper suggests pursuing a strategy of diversity concerning the approaches to shape the bioeconomy, the funding of research topics, and the involvement of stakeholders.

  9. Identification of Metabolic Pathway Systems.

    Science.gov (United States)

    Dolatshahi, Sepideh; Voit, Eberhard O

    2016-01-01

    The estimation of parameters in even moderately large biological systems is a significant challenge. This challenge is greatly exacerbated if the mathematical formats of appropriate process descriptions are unknown. To address this challenge, the method of dynamic flux estimation (DFE) was proposed for the analysis of metabolic time series data. Under ideal conditions, the first phase of DFE yields numerical representations of all fluxes within a metabolic pathway system, either as values at each time point or as plots against their substrates and modulators. However, this numerical result does not reveal the mathematical format of each flux. Thus, the second phase of DFE selects functional formats that are consistent with the numerical trends obtained from the first phase. While greatly facilitating metabolic data analysis, DFE is only directly applicable if the pathway system contains as many dependent variables as fluxes. Because most actual systems contain more fluxes than metabolite pools, this requirement is seldom satisfied. Auxiliary methods have been proposed to alleviate this issue, but they are not general. Here we propose strategies that extend DFE toward general, slightly underdetermined pathway systems.

  10. The updated RGD Pathway Portal utilizes increased curation efficiency and provides expanded pathway information.

    Science.gov (United States)

    Hayman, G Thomas; Jayaraman, Pushkala; Petri, Victoria; Tutaj, Marek; Liu, Weisong; De Pons, Jeff; Dwinell, Melinda R; Shimoyama, Mary

    2013-02-05

    The RGD Pathway Portal provides pathway annotations for rat, human and mouse genes and pathway diagrams and suites, all interconnected via the pathway ontology. Diagram pages present the diagram and description, with diagram objects linked to additional resources. A newly-developed dual-functionality web application composes the diagram page. Curators input the description, diagram, references and additional pathway objects. The application combines these with tables of rat, human and mouse pathway genes, including genetic information, analysis tool and reference links, and disease, phenotype and other pathway annotations to pathway genes. The application increases the information content of diagram pages while expediting publication.

  11. KEGG PATHWAY / Acute myeloid leukemia [KEGG

    Lifescience Database Archive (English)

    Full Text Available PATHWAY: map05221 Entry map05221Pathway Name Acute myeloid leukemia Description Acute...Class Human Diseases; Cancers Pathwaymap map05221Acute myeloid leukemia Disease H00003Acute myeloid leukemia...inkDB DBGET integrated database retrieval system KEGG PATHWAY / Acute myeloid leukemia ...

  12. A brain cancer pathway in clinical practice

    DEFF Research Database (Denmark)

    Laursen, Emilie Lund; Rasmussen, Birthe Krogh

    2012-01-01

    Danish healthcare seeks to improve cancer survival through improved diagnostics, rapid treatment and increased focus on cancer prevention and early help-seeking. In neuro-oncology, this has resulted in the Integrated Brain Cancer Pathway (IBCP). The paper explores how the pathway works...... in the initial phase in a clinical setting with emphasis on pathway criteria....

  13. Primary Metabolic Pathways and Metabolic Flux Analysis

    DEFF Research Database (Denmark)

    2015-01-01

    his chapter introduces the metabolic flux analysis (MFA) or stoichiometry-based MFA, and describes the quantitative basis for MFA. It discusses the catabolic pathways in which free energy is produced to drive the cell-building anabolic pathways. An overview of these primary pathways provides...

  14. Apoptotic engulfment pathway and schizophrenia.

    Directory of Open Access Journals (Sweden)

    Xiangning Chen

    Full Text Available BACKGROUND: Apoptosis has been speculated to be involved in schizophrenia. In a previously study, we reported the association of the MEGF10 gene with the disease. In this study, we followed the apoptotic engulfment pathway involving the MEGF10, GULP1, ABCA1 and ABCA7 genes and tested their association with the disease. METHODOLOGY/PRINCIPAL FINDINGS: Ten, eleven and five SNPs were genotyped in the GULP1, ABCA1 and ABCA7 genes respectively for the ISHDSF and ICCSS samples. In all 3 genes, we observed nominally significant associations. Rs2004888 at GULP1 was significant in both ISHDSF and ICCSS samples (p = 0.0083 and 0.0437 respectively. We sought replication in independent samples for this marker and found highly significant association (p = 0.0003 in 3 Caucasian replication samples. But it was not significant in the 2 Chinese replication samples. In addition, we found a significant 2-marker (rs2242436 * rs3858075 interaction between the ABCA1 and ABCA7 genes in the ISHDSF sample (p = 0.0022 and a 3-marker interaction (rs246896 * rs4522565 * rs3858075 amongst the MEGF10, GULP1 and ABCA1 genes in the ICCSS sample (p = 0.0120. Rs3858075 in the ABCA1 gene was involved in both 2- and 3-marker interactions in the two samples. CONCLUSIONS/SIGNIFICANCE: From these data, we concluded that the GULP1 gene and the apoptotic engulfment pathway are involved in schizophrenia in subjects of European ancestry and multiple genes in the pathway may interactively increase the risks to the disease.

  15. Apoptotic engulfment pathway and schizophrenia.

    LENUS (Irish Health Repository)

    Chen, Xiangning

    2009-01-01

    BACKGROUND: Apoptosis has been speculated to be involved in schizophrenia. In a previously study, we reported the association of the MEGF10 gene with the disease. In this study, we followed the apoptotic engulfment pathway involving the MEGF10, GULP1, ABCA1 and ABCA7 genes and tested their association with the disease. METHODOLOGY\\/PRINCIPAL FINDINGS: Ten, eleven and five SNPs were genotyped in the GULP1, ABCA1 and ABCA7 genes respectively for the ISHDSF and ICCSS samples. In all 3 genes, we observed nominally significant associations. Rs2004888 at GULP1 was significant in both ISHDSF and ICCSS samples (p = 0.0083 and 0.0437 respectively). We sought replication in independent samples for this marker and found highly significant association (p = 0.0003) in 3 Caucasian replication samples. But it was not significant in the 2 Chinese replication samples. In addition, we found a significant 2-marker (rs2242436 * rs3858075) interaction between the ABCA1 and ABCA7 genes in the ISHDSF sample (p = 0.0022) and a 3-marker interaction (rs246896 * rs4522565 * rs3858075) amongst the MEGF10, GULP1 and ABCA1 genes in the ICCSS sample (p = 0.0120). Rs3858075 in the ABCA1 gene was involved in both 2- and 3-marker interactions in the two samples. CONCLUSIONS\\/SIGNIFICANCE: From these data, we concluded that the GULP1 gene and the apoptotic engulfment pathway are involved in schizophrenia in subjects of European ancestry and multiple genes in the pathway may interactively increase the risks to the disease.

  16. New clinical pathways for keratoconus

    Science.gov (United States)

    Gore, D M; Shortt, A J; Allan, B D

    2013-01-01

    Pre-2000, the clinical management of keratoconus centred on rigid contact lens fitting when spectacle corrected acuity was no longer adequate, and transplantation where contact lens wear failed. Over the last decade, outcome data have accumulated for new interventions including corneal collagen crosslinking, intracorneal ring implantation, topographic phototherapeutic keratectomy, and phakic intraocular lens implantation. We review the current evidence base for these interventions and their place in new management pathways for keratoconus under two key headings: corneal shape stabilisation and visual rehabilitation. PMID:23258309

  17. Fibromyalgia and the serotonin pathway.

    Science.gov (United States)

    Juhl, J H

    1998-10-01

    Fibromyalgia syndrome is a musculoskeletal pain and fatigue disorder manifested by diffuse myalgia, localized areas of tenderness, fatigue, lowered pain thresholds, and nonrestorative sleep. Evidence from multiple sources support the concept of decreased flux through the serotonin pathway in fibromyalgia patients. Serotonin substrate supplementation, via L-tryptophan or 5-hydroxytryptophan (5-HTP), has been shown to improve symptoms of depression, anxiety, insomnia and somatic pains in a variety of patient cohorts. Identification of low serum tryptophan and serotonin levels may be a simple way to identify persons who will respond well to this approach.

  18. Oxylipin Pathway in Rice and Arabidopsis

    Institute of Scientific and Technical Information of China (English)

    E. Wassim Chehab; John V. Perea; Banu Gopalan; Steve Theg; Katayoon Dehesh

    2007-01-01

    Plants have evolved complex signaling pathways to coordinate responses to developmental and environmental information. The oxylipin pathway is one pivotal lipid-based signaling network, composed of several competing branch pathways, that determines the plant's ability to adapt to various stimuli. Activation of the oxylipin pathway induces the de novo synthesis of biologically active metabolltes called "oxylipins". The relative levels of these metabolltes are a distinct indicator of each plant species and determine the ability of plants to adapt to different stimuli. The two major branches of the oxylipln pathway, allene oxide synthase (AOS) and hydroperoxide lyase (HPL) are responsible for production of the signaling compounds,jasmonates and aldehydes respectively. Here, we compare and contrast the regulation of AOS and HPL branch pathways in rice and Arabidopsis as model monocotyledonous and dicotyledonous systems. These analyses provide new Insights into the evolution of JAs and aldehydes signaling pathways, and the complex network of processes responsible for stress adaptations in monocots and dicots.

  19. Combustion kinetics and reaction pathways

    Energy Technology Data Exchange (ETDEWEB)

    Klemm, R.B.; Sutherland, J.W. [Brookhaven National Laboratory, Upton, NY (United States)

    1993-12-01

    This project is focused on the fundamental chemistry of combustion. The overall objectives are to determine rate constants for elementary reactions and to elucidate the pathways of multichannel reactions. A multitechnique approach that features three independent experiments provides unique capabilities in performing reliable kinetic measurements over an exceptionally wide range in temperature, 300 to 2500 K. Recent kinetic work has focused on experimental studies and theoretical calculations of the methane dissociation system (CH{sub 4} + Ar {yields} CH{sub 3} + H + Ar and H + CH{sub 4} {yields} CH{sub 3} + H{sub 2}). Additionally, a discharge flow-photoionization mass spectrometer (DF-PIMS) experiment is used to determine branching fractions for multichannel reactions and to measure ionization thresholds of free radicals. Thus, these photoionization experiments generate data that are relevant to both reaction pathways studies (reaction dynamics) and fundamental thermochemical research. Two distinct advantages of performing PIMS with high intensity, tunable vacuum ultraviolet light at the National Synchrotron Light Source are high detection sensitivity and exceptional selectivity in monitoring radical species.

  20. Central neural pathways for thermoregulation

    Science.gov (United States)

    Morrison, Shaun F.; Nakamura, Kazuhiro

    2010-01-01

    Central neural circuits orchestrate a homeostatic repertoire to maintain body temperature during environmental temperature challenges and to alter body temperature during the inflammatory response. This review summarizes the functional organization of the neural pathways through which cutaneous thermal receptors alter thermoregulatory effectors: the cutaneous circulation for heat loss, the brown adipose tissue, skeletal muscle and heart for thermogenesis and species-dependent mechanisms (sweating, panting and saliva spreading) for evaporative heat loss. These effectors are regulated by parallel but distinct, effector-specific neural pathways that share a common peripheral thermal sensory input. The thermal afferent circuits include cutaneous thermal receptors, spinal dorsal horn neurons and lateral parabrachial nucleus neurons projecting to the preoptic area to influence warm-sensitive, inhibitory output neurons which control thermogenesis-promoting neurons in the dorsomedial hypothalamus that project to premotor neurons in the rostral ventromedial medulla, including the raphe pallidus, that descend to provide the excitation necessary to drive thermogenic thermal effectors. A distinct population of warm-sensitive preoptic neurons controls heat loss through an inhibitory input to raphe pallidus neurons controlling cutaneous vasoconstriction. PMID:21196160

  1. Pathways towards ferroelectricity in hafnia

    Science.gov (United States)

    Huan, Tran Doan; Sharma, Vinit; Rossetti, George A.; Ramprasad, Rampi

    2014-08-01

    The question of whether one can systematically identify (previously unknown) ferroelectric phases of a given material is addressed, taking hafnia (HfO2) as an example. Low free energy phases at various pressures and temperatures are identified using a first-principles based structure search algorithm. Ferroelectric phases are then recognized by exploiting group theoretical principles for the symmetry-allowed displacive transitions between nonpolar and polar phases. Two orthorhombic polar phases occurring in space groups Pca21 and Pmn21 are singled out as the most viable ferroelectric phases of hafnia, as they display low free energies (relative to known nonpolar phases), and substantial switchable spontaneous electric polarization. These results provide an explanation for the recently observed surprising ferroelectric behavior of hafnia, and reveal pathways for stabilizing ferroelectric phases of hafnia as well as other compounds.

  2. Post-Communist Welfare Pathways

    DEFF Research Database (Denmark)

    Cerami, Alfio; Vanhuysse, Pieter

    This collection adopts novel theoretical approaches to study the diverse welfare state pathways that have evolved across Central and Eastern Europe since the fall of communism in 1989. Going beyond existing path dependency and neo-institutionalist explanations, it highlights the role of explanatory...... factors such as micro-causal mechanisms, ideas, discourses, path departures, power politics, and elite strategies. This book includes contributions from leading international Experts such as Claus Offe, Robert Kaufman, Stefan Haggard, Tomasz Inglot, and Mitchell Orenstein, to examine welfare in specific...... or oppose reform, and national or supranational ideas and discourse that frame those reform efforts.' - Vivien A. Schmidt, Jean Monnet Professor of European Integration, Boston University ‘Quite an extraordinary book. One rarely reads an edited volume in which contributors engage each other the way they do...

  3. Longevity pathways and memory ageing

    Directory of Open Access Journals (Sweden)

    Ilias eGkikas

    2014-06-01

    Full Text Available The ageing process has been associated with numerous pathologies at the cellular, tissue, and organ level. Decline or loss of brain functions, including learning and memory, is one of the most devastating and feared aspects of ageing. Learning and memory are fundamental processes by which animals adjust to environmental changes, evaluate various sensory signals based on context and experience, and make decisions to generate adaptive behaviours. Age-related memory impairment is an important phenotype of brain ageing. Understanding the molecular mechanisms underlying age-related memory impairment is crucial for the development of therapeutic strategies that may eventually lead to the development of drugs to combat memory loss. Studies in invertebrate animal models have taught us much about the physiology of ageing and its effects on learning and memory. In this review we survey recent progress relevant to conserved molecular pathways implicated in both ageing and memory formation and consolidation.

  4. The SUMO Pathway in Mitosis.

    Science.gov (United States)

    Mukhopadhyay, Debaditya; Dasso, Mary

    2017-01-01

    Mitosis is the stage of the cell cycle during which replicated chromosomes must be precisely divided to allow the formation of two daughter cells possessing equal genetic material. Much of the careful spatial and temporal organization of mitosis is maintained through post-translational modifications, such as phosphorylation and ubiquitination, of key cellular proteins. Here, we will review evidence that sumoylation, conjugation to the SUMO family of small ubiquitin-like modifiers, also serves essential regulatory roles during mitosis. We will discuss the basic biology of sumoylation, how the SUMO pathway has been implicated in particular mitotic functions, including chromosome condensation, centromere/kinetochore organization and cytokinesis, and what cellular proteins may be the targets underlying these phenomena.

  5. Signalling pathways in pemphigus vulgaris.

    Science.gov (United States)

    Li, Xiaoguang; Ishii, Norito; Ohata, Chika; Furumura, Minao; Hashimoto, Takashi

    2014-03-01

    Acantholysis in pemphigus vulgaris is induced by binding of autoantibodies to desmoglein 3 (Dsg3). The roles of signalling pathways on development of acantholysis have recently been extensively studied. In the study by Sayar et al., recently published in Exp Dermatol, epidermal growth factor receptor (EGFR) signalling was activated in both in vivo and in vitro pemphigus vulgaris experimental models. However, while EGFR inhibitors suppressed activity of p38 mitogen-activated protein kinase (p38MAPK) linearly, they suppressed activity of c-Myc and acantholysis in a non-linear, V-shaped relationship. These findings indicated complicated interactions among EGFR, p38MAPK and c-Myc in pemphigus vulgaris pathology.

  6. Changing Arctic Ocean freshwater pathways.

    Science.gov (United States)

    Morison, James; Kwok, Ron; Peralta-Ferriz, Cecilia; Alkire, Matt; Rigor, Ignatius; Andersen, Roger; Steele, Mike

    2012-01-04

    Freshening in the Canada basin of the Arctic Ocean began in the 1990s and continued to at least the end of 2008. By then, the Arctic Ocean might have gained four times as much fresh water as comprised the Great Salinity Anomaly of the 1970s, raising the spectre of slowing global ocean circulation. Freshening has been attributed to increased sea ice melting and contributions from runoff, but a leading explanation has been a strengthening of the Beaufort High--a characteristic peak in sea level atmospheric pressure--which tends to accelerate an anticyclonic (clockwise) wind pattern causing convergence of fresh surface water. Limited observations have made this explanation difficult to verify, and observations of increasing freshwater content under a weakened Beaufort High suggest that other factors must be affecting freshwater content. Here we use observations to show that during a time of record reductions in ice extent from 2005 to 2008, the dominant freshwater content changes were an increase in the Canada basin balanced by a decrease in the Eurasian basin. Observations are drawn from satellite data (sea surface height and ocean-bottom pressure) and in situ data. The freshwater changes were due to a cyclonic (anticlockwise) shift in the ocean pathway of Eurasian runoff forced by strengthening of the west-to-east Northern Hemisphere atmospheric circulation characterized by an increased Arctic Oscillation index. Our results confirm that runoff is an important influence on the Arctic Ocean and establish that the spatial and temporal manifestations of the runoff pathways are modulated by the Arctic Oscillation, rather than the strength of the wind-driven Beaufort Gyre circulation.

  7. Fuel Dependence of Benzene Pathways

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, H; Eddings, E; Sarofim, A; Westbrook, C

    2008-07-14

    The relative importance of formation pathways for benzene, an important precursor to soot formation, was determined from the simulation of 22 premixed flames for a wide range of equivalence ratios (1.0 to 3.06), fuels (C{sub 1}-C{sub 12}), and pressures (20 to 760 torr). The maximum benzene concentrations in 15 out of these flames were well reproduced within 30% of the experimental data. Fuel structural properties were found to be critical for benzene production. Cyclohexanes and C{sub 3} and C{sub 4} fuels were found to be among the most productive in benzene formation; and long-chain normal paraffins produce the least amount of benzene. Other properties, such as equivalence ratio and combustion temperatures, were also found to be important in determining the amount of benzene produced in flames. Reaction pathways for benzene formation were examined critically in four premixed flames of structurally different fuels of acetylene, n-decane, butadiene, and cyclohexane. Reactions involving precursors, such as C{sub 3} and C{sub 4} species, were examined. Combination reactions of C{sub 3} species were identified to be the major benzene formation routes with the exception of the cyclohexane flame, in which benzene is formed exclusively from cascading fuel dehydrogenation via cyclohexene and cyclohexadiene intermediates. Acetylene addition makes a minor contribution to benzene formation, except in the butadiene flame where C{sub 4}H{sub 5} radicals are produced directly from the fuel, and in the n-decane flame where C{sub 4}H{sub 5} radicals are produced from large alkyl radical decomposition and H atom abstraction from the resulting large olefins.

  8. The pathway ontology - updates and applications.

    Science.gov (United States)

    Petri, Victoria; Jayaraman, Pushkala; Tutaj, Marek; Hayman, G Thomas; Smith, Jennifer R; De Pons, Jeff; Laulederkind, Stanley Jf; Lowry, Timothy F; Nigam, Rajni; Wang, Shur-Jen; Shimoyama, Mary; Dwinell, Melinda R; Munzenmaier, Diane H; Worthey, Elizabeth A; Jacob, Howard J

    2014-02-05

    The Pathway Ontology (PW) developed at the Rat Genome Database (RGD), covers all types of biological pathways, including altered and disease pathways and captures the relationships between them within the hierarchical structure of a directed acyclic graph. The ontology allows for the standardized annotation of rat, and of human and mouse genes to pathway terms. It also constitutes a vehicle for easy navigation between gene and ontology report pages, between reports and interactive pathway diagrams, between pathways directly connected within a diagram and between those that are globally related in pathway suites and suite networks. Surveys of the literature and the development of the Pathway and Disease Portals are important sources for the ongoing development of the ontology. User requests and mapping of pathways in other databases to terms in the ontology further contribute to increasing its content. Recently built automated pipelines use the mapped terms to make available the annotations generated by other groups. The two released pipelines - the Pathway Interaction Database (PID) Annotation Import Pipeline and the Kyoto Encyclopedia of Genes and Genomes (KEGG) Annotation Import Pipeline, make available over 7,400 and 31,000 pathway gene annotations, respectively. Building the PID pipeline lead to the addition of new terms within the signaling node, also augmented by the release of the RGD "Immune and Inflammatory Disease Portal" at that time. Building the KEGG pipeline lead to a substantial increase in the number of disease pathway terms, such as those within the 'infectious disease pathway' parent term category. The 'drug pathway' node has also seen increases in the number of terms as well as a restructuring of the node. Literature surveys, disease portal deployments and user requests have contributed and continue to contribute additional new terms across the ontology. Since first presented, the content of PW has increased by over 75%. Ongoing development of

  9. Pathway-Based Functional Analysis of Metagenomes

    Science.gov (United States)

    Bercovici, Sivan; Sharon, Itai; Pinter, Ron Y.; Shlomi, Tomer

    Metagenomic data enables the study of microbes and viruses through their DNA as retrieved directly from the environment in which they live. Functional analysis of metagenomes explores the abundance of gene families, pathways, and systems, rather than their taxonomy. Through such analysis researchers are able to identify those functional capabilities most important to organisms in the examined environment. Recently, a statistical framework for the functional analysis of metagenomes was described that focuses on gene families. Here we describe two pathway level computational models for functional analysis that take into account important, yet unaddressed issues such as pathway size, gene length and overlap in gene content among pathways. We test our models over carefully designed simulated data and propose novel approaches for performance evaluation. Our models significantly improve over current approach with respect to pathway ranking and the computations of relative abundance of pathways in environments.

  10. Reconstructing fungal natural product biosynthetic pathways.

    Science.gov (United States)

    Lazarus, C M; Williams, K; Bailey, A M

    2014-10-01

    Large scale fungal genome sequencing has revealed a multitude of potential natural product biosynthetic pathways that remain uncharted. Here we describe some of the methods that have been used to explore them via heterologous gene expression. We focus on filamentous fungal hosts and discuss the technological challenges and successes behind the reconstruction of fungal natural product pathways. Optimised, efficient heterologous expression of reconstructed biosynthetic pathways promises progress in the discovery of novel compounds that could be utilised by the pharmaceutical and agrochemical industries.

  11. Coherent band pathways between knots and links

    CERN Document Server

    Buck, Dorothy

    2014-01-01

    We categorise coherent band (aka nullification) pathways between knots and 2-component links. Additionally, we characterise the minimal coherent band pathways (with intermediates) between any two knots or 2-component links with small crossing number. We demonstrate these band surgeries for knots and links with small crossing number. We apply these results to place lower bounds on the minimum number of recombinant events separating DNA configurations, restrict the recombination pathways and determine chirality and/or orientation of the resulting recombinant DNA molecules.

  12. Method for determining heterologous biosynthesis pathways

    KAUST Repository

    Gao, Xin

    2017-08-10

    The present invention relates to a method and system for dynamically analyzing, determining, predicting and displaying ranked suitable heterologous biosynthesis pathways for a specified host. The present invention addresses the problem of finding suitable pathways for the endogenous metabolism of a host organism because the efficacy of heterologous biosynthesis is affected by competing endogenous pathways. The present invention is called MRE (Metabolic Route Explorer), and it was conceived and developed to systematically and dynamically search for, determine, analyze, and display promising heterologous pathways while considering competing endogenous reactions in a given host organism.

  13. Effects of PDT on the endocytic pathway

    Science.gov (United States)

    Kessel, David

    2010-02-01

    Two lines of evidence point to an early effect of photodamage on membrane trafficking. [1] Internalization of a fluorescent probe for hydrophobic membrane loci was impaired by prior photodamage. [2] Interference with the endocytic pathway by the PI-3 kinase antagonist wortmannin led to accumulation of cytoplasmic vacuoles suggesting a block in the recycling of plasma membrane components. Prior photodamage blocked this pathway so that no vacuoles were formed upon exposure of cells to wortmannin. In a murine hepatoma line, the endocytic pathway was preferentially sensitive to lysosomal photodamage. The role of photodamage to the endocytic pathway as a factor in PDT efficacy remains to be assessed.

  14. Female offenders’ pathways to prison in Belgium

    Directory of Open Access Journals (Sweden)

    Nuytiens An

    2012-01-01

    Full Text Available This paper examines some results of a research on female offenders’ life histories and pathways to prison in Belgium. Women’s pathways into crime will be presented and the connection of these pathways to their life histories will be explored. The study reveals that the greater part of the research population are adult-onset offenders. The authors argue that the importance of adult-onset pathways for female offenders might be explained by the emergence of (gendered vulnerabilities within the women’s lives, often accumulated not before adulthood.

  15. Correcting ligands, metabolites, and pathways

    Directory of Open Access Journals (Sweden)

    Vriend Gert

    2006-11-01

    Full Text Available Abstract Background A wide range of research areas in bioinformatics, molecular biology and medicinal chemistry require precise chemical structure information about molecules and reactions, e.g. drug design, ligand docking, metabolic network reconstruction, and systems biology. Most available databases, however, treat chemical structures more as illustrations than as a datafield in its own right. Lack of chemical accuracy impedes progress in the areas mentioned above. We present a database of metabolites called BioMeta that augments the existing pathway databases by explicitly assessing the validity, correctness, and completeness of chemical structure and reaction information. Description The main bulk of the data in BioMeta were obtained from the KEGG Ligand database. We developed a tool for chemical structure validation which assesses the chemical validity and stereochemical completeness of a molecule description. The validation tool was used to examine the compounds in BioMeta, showing that a relatively small number of compounds had an incorrect constitution (connectivity only, not considering stereochemistry and that a considerable number (about one third had incomplete or even incorrect stereochemistry. We made a large effort to correct the errors and to complete the structural descriptions. A total of 1468 structures were corrected and/or completed. We also established the reaction balance of the reactions in BioMeta and corrected 55% of the unbalanced (stoichiometrically incorrect reactions in an automatic procedure. The BioMeta database was implemented in PostgreSQL and provided with a web-based interface. Conclusion We demonstrate that the validation of metabolite structures and reactions is a feasible and worthwhile undertaking, and that the validation results can be used to trigger corrections and improvements to BioMeta, our metabolite database. BioMeta provides some tools for rational drug design, reaction searches, and

  16. Computing Pathways for Urban Decarbonization.

    Science.gov (United States)

    Cremades, R.; Sommer, P.

    2016-12-01

    Urban areas emit roughly three quarters of global carbon emissions. Cities are crucial elements for a decarbonized society. Urban expansion and related transportation needs lead to increased energy use, and to carbon-intensive lock-ins that create barriers for climate change mitigation globally. The authors present the Integrated Urban Complexity (IUC) model, based on self-organizing Cellular Automata (CA), and use it to produce a new kind of spatially explicit Transformation Pathways for Urban Decarbonization (TPUD). IUC is based on statistical evidence relating the energy needed for transportation with the spatial distribution of population, specifically IUC incorporates variables from complexity science related to urban form, like the slope of the rank-size rule or spatial entropy, which brings IUC a step beyond existing models. The CA starts its evolution with real-world urban land use and population distribution data from the Global Human Settlement Layer. Thus, the IUC model runs over existing urban settlements, transforming the spatial distribution of population so the energy consumption for transportation is minimized. The statistical evidence that governs the evolution of the CA departs from the database of the International Association of Public Transport. A selected case is presented using Stuttgart (Germany) as an example. The results show how IUC varies urban density in those places where it improves the performance of crucial parameters related to urban form, producing a TPUD that shows where the spatial distribution of population should be modified with a degree of detail of 250 meters of cell size. The TPUD shows how the urban complex system evolves over time to minimize energy consumption for transportation. The resulting dynamics or urban decarbonization show decreased energy per capita, although total energy increases for increasing population. The results provide innovative insights: by checking current urban planning against a TPUD, urban

  17. The pathway ontology – updates and applications

    Science.gov (United States)

    2014-01-01

    Background The Pathway Ontology (PW) developed at the Rat Genome Database (RGD), covers all types of biological pathways, including altered and disease pathways and captures the relationships between them within the hierarchical structure of a directed acyclic graph. The ontology allows for the standardized annotation of rat, and of human and mouse genes to pathway terms. It also constitutes a vehicle for easy navigation between gene and ontology report pages, between reports and interactive pathway diagrams, between pathways directly connected within a diagram and between those that are globally related in pathway suites and suite networks. Surveys of the literature and the development of the Pathway and Disease Portals are important sources for the ongoing development of the ontology. User requests and mapping of pathways in other databases to terms in the ontology further contribute to increasing its content. Recently built automated pipelines use the mapped terms to make available the annotations generated by other groups. Results The two released pipelines – the Pathway Interaction Database (PID) Annotation Import Pipeline and the Kyoto Encyclopedia of Genes and Genomes (KEGG) Annotation Import Pipeline, make available over 7,400 and 31,000 pathway gene annotations, respectively. Building the PID pipeline lead to the addition of new terms within the signaling node, also augmented by the release of the RGD “Immune and Inflammatory Disease Portal” at that time. Building the KEGG pipeline lead to a substantial increase in the number of disease pathway terms, such as those within the ‘infectious disease pathway’ parent term category. The ‘drug pathway’ node has also seen increases in the number of terms as well as a restructuring of the node. Literature surveys, disease portal deployments and user requests have contributed and continue to contribute additional new terms across the ontology. Since first presented, the content of PW has increased by

  18. Machine learning methods for metabolic pathway prediction

    Directory of Open Access Journals (Sweden)

    Karp Peter D

    2010-01-01

    Full Text Available Abstract Background A key challenge in systems biology is the reconstruction of an organism's metabolic network from its genome sequence. One strategy for addressing this problem is to predict which metabolic pathways, from a reference database of known pathways, are present in the organism, based on the annotated genome of the organism. Results To quantitatively validate methods for pathway prediction, we developed a large "gold standard" dataset of 5,610 pathway instances known to be present or absent in curated metabolic pathway databases for six organisms. We defined a collection of 123 pathway features, whose information content we evaluated with respect to the gold standard. Feature data were used as input to an extensive collection of machine learning (ML methods, including naïve Bayes, decision trees, and logistic regression, together with feature selection and ensemble methods. We compared the ML methods to the previous PathoLogic algorithm for pathway prediction using the gold standard dataset. We found that ML-based prediction methods can match the performance of the PathoLogic algorithm. PathoLogic achieved an accuracy of 91% and an F-measure of 0.786. The ML-based prediction methods achieved accuracy as high as 91.2% and F-measure as high as 0.787. The ML-based methods output a probability for each predicted pathway, whereas PathoLogic does not, which provides more information to the user and facilitates filtering of predicted pathways. Conclusions ML methods for pathway prediction perform as well as existing methods, and have qualitative advantages in terms of extensibility, tunability, and explainability. More advanced prediction methods and/or more sophisticated input features may improve the performance of ML methods. However, pathway prediction performance appears to be limited largely by the ability to correctly match enzymes to the reactions they catalyze based on genome annotations.

  19. Robust de novo pathway enrichment with KeyPathwayMiner 5

    DEFF Research Database (Denmark)

    Alcaraz, Nicolas; List, Markus; Dissing-Hansen, Martin

    2016-01-01

    Identifying functional modules or novel active pathways, recently termed de novo pathway enrichment, is a computational systems biology challenge that has gained much attention during the last decade. Given a large biological interaction network, KeyPathwayMiner extracts connected subnetworks...... several network perturbation techniques and over a range of perturbation degrees. In addition, users may now provide a gold-standard set to determine how enriched extracted pathways are with relevant genes compared to randomized versions of the original network....

  20. The calcium oxotellurate(IV) nitrates Ca5Te4O12(NO3)2(H2O)2 and Ca6Te5O15(NO3)2 . Non-classic order/disorder polytypism and a rigid framework structure

    Science.gov (United States)

    Stöger, Berthold; Weil, Matthias

    2013-04-01

    Single crystals of two novel calcium oxotellurate(IV) nitrates were grown under hydrothermal conditions and were structurally characterized by X-ray diffraction. Ca_5Te_4{O}_{12}(NO_3)_2(H_2O)_2 [Cc, Z=4, a=25.258(3) Å, b=5.7289(7) Å, c=17.0066(19) Å, β =124.377(2)°, R[F^2 > 2σ (F^2)]=0.043, 4083 F^2 data, 281 parameters] can be described as a non-classic order/disorder (OD) structure, which fulfills the basic principle of OD theory, viz. local equivalence of polytypes, but does not strictly follow the vicinity condition (VC) of OD theory. The structure is made up from an alternating stacking of non-polar layers composed of isolated [TeO_3] units and Ca^{2+} ions and polar layers containing NO_3^- ions and water molecules. The electron lone-pairs of the [TeO_3] units protrude into the free space of the anion/water layers. The crystal under investigation was a non-classic OD-twin of domains of a maximum degree of order (MDO). At the twin plane a fragment of the second MDO polytype is located. The main building blocks of Ca_6Te_5{O}_{15}(NO_3)_2 [P2_1/c, Z=4, a=15.494(2) Å, b=5.6145(7) Å, c=39.338(4) Å, β =142.480(5)°, R[F^2 > 2σ (F^2)]=0.043, 3026 F^2 data, 307 parameters] are isolated [TeO_3] units and Ca^{2+} ions which are connected to a three-dimensional framework perforated by channels in which the N atoms of the nitrate anions are located and the electron lone-pairs of the [TeO_3] units protrude. The structure can topologically be derived from the structure of Ca_5Te_4{O}_{12}(NO_3)_2(H_2O)_2 by removing the water molecules and connecting the CaTeO_3 layers with additional [TeO_3] units and Ca^{2+} ions.

  1. Melanin biosynthesis pathway in Agaricus bisporus mushrooms

    NARCIS (Netherlands)

    Weijn, A.; Bastiaan-Net, S.; Wichers, H.J.; Mes, J.J.

    2013-01-01

    With the full genome sequence of Agaricus bisporus available, it was possible to investigate the genes involved in the melanin biosynthesis pathway of button mushrooms. Based on different BLAST and alignments, genes were identified in the genome which are postulated to be involved in this pathway.

  2. Mining the Wnt pathway for cancer therapeutics.

    NARCIS (Netherlands)

    Barker, N.; Clevers, J.C.

    2006-01-01

    Aberrant activation of the Wnt pathway is implicated in driving the formation of various human cancers, particularly those of the digestive tract. Inhibition of aberrant Wnt pathway activity in cancer cell lines efficiently blocks their growth, highlighting the great potential of therapeutics design

  3. Modeling cancer progression via pathway dependencies.

    Directory of Open Access Journals (Sweden)

    Elena J Edelman

    2008-02-01

    Full Text Available Cancer is a heterogeneous disease often requiring a complexity of alterations to drive a normal cell to a malignancy and ultimately to a metastatic state. Certain genetic perturbations have been implicated for initiation and progression. However, to a great extent, underlying mechanisms often remain elusive. These genetic perturbations are most likely reflected by the altered expression of sets of genes or pathways, rather than individual genes, thus creating a need for models of deregulation of pathways to help provide an understanding of the mechanisms of tumorigenesis. We introduce an integrative hierarchical analysis of tumor progression that discovers which a priori defined pathways are relevant either throughout or in particular steps of progression. Pathway interaction networks are inferred for these relevant pathways over the steps in progression. This is followed by the refinement of the relevant pathways to those genes most differentially expressed in particular disease stages. The final analysis infers a gene interaction network for these refined pathways. We apply this approach to model progression in prostate cancer and melanoma, resulting in a deeper understanding of the mechanisms of tumorigenesis. Our analysis supports previous findings for the deregulation of several pathways involved in cell cycle control and proliferation in both cancer types. A novel finding of our analysis is a connection between ErbB4 and primary prostate cancer.

  4. Optic pathway degeneration in Japanese black cattle.

    Science.gov (United States)

    Chiba, Shiori; Funato, Shingo; Horiuchi, Noriyuki; Matsumoto, Kotaro; Inokuma, Hisashi; Furuoka, Hidefumi; Kobayashi, Yoshiyasu

    2015-02-01

    Degeneration of the optic pathway has been reported in various animal species including cattle. We experienced a case of bilateral optic tract degeneration characterized by severe gliosis in a Japanese black cattle without any obvious visual defects. To evaluate the significance, pathological nature and pathogenesis of the lesions, we examined the optic pathway in 60 cattle (41 Japanese black, 13 Holstein and 6 crossbreed) with or without ocular abnormalities. None of these animals had optic canal stenosis. Degenerative changes with severe gliosis in the optic pathway, which includes the optic nerve, optic chiasm and optic tract, were only observed in 8 Japanese black cattle with or without ocular abnormalities. Furthermore, strong immunoreactivity of glial fibrillary acidic protein was observed in the retinal stratum opticum and ganglion cell layer in all 5 cattle in which the optic pathway lesions could be examined. As etiological research, we also examined whether the concentrations of vitamin A and vitamin B12 or bovine viral diarrhea virus (BVDV) infection was associated with optic pathway degeneration. However, our results suggested that the observed optic pathway degeneration was probably not caused by these factors. These facts indicate the presence of optic pathway degeneration characterized by severe gliosis that has never been reported in cattle without bilateral compressive lesions in the optic pathway or bilateral severe retinal atrophy.

  5. Fuel Pathway Integration Technical Team Roadmap

    Energy Technology Data Exchange (ETDEWEB)

    None

    2013-06-01

    The Fuel Pathway Integration Technical Team (FPITT) supports the U.S. DRIVE Partnership (the Partnership) in the identification and evaluation of implementation scenarios for fuel cell technology pathways, including hydrogen and fuel cell electric vehicles in the transportation sector, both during a transition period and in the long term.

  6. Opportunities for pharmaceutical care with critical pathways.

    Science.gov (United States)

    Koch, K E

    1995-01-01

    Critical pathways are multidisciplinary tools designed to improve patient care and efficiency. Almost every path requires some type of pharmacotherapeutic intervention, from selection of surgical prophylaxis to management of anticoagulation. Pharmacists should become involved with the critical pathway process because it offers an excellent opportunity to incorporate pharmaceutical care and to meet Joint Commission on Accreditation of Healthcare Organization compliance criteria.

  7. Calcium influx pathways in rat pancreatic ducts

    DEFF Research Database (Denmark)

    Hug, M J; Pahl, C; Novak, I

    1996-01-01

    A number of agonists increase intracellular Ca2+ activity, [Ca2+]i, in pancreatic ducts, but the influx/efflux pathways and intracellular Ca2+ stores in this epithelium are unknown. The aim of the present study was to characterise the Ca2+ influx pathways, especially their pH sensitivity, in nati...

  8. A brain cancer pathway in clinical practice

    DEFF Research Database (Denmark)

    Laursen, Emilie Lund; Rasmussen, Birthe Krogh

    2012-01-01

    Danish healthcare seeks to improve cancer survival through improved diagnostics, rapid treatment and increased focus on cancer prevention and early help-seeking. In neuro-oncology, this has resulted in the Integrated Brain Cancer Pathway (IBCP). The paper explores how the pathway works...

  9. DMPD: Parallel pathways of virus recognition. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 16713969 Parallel pathways of virus recognition. Tenoever BR, Maniatis T. Immunity.... 2006 May;24(5):510-2. (.png) (.svg) (.html) (.csml) Show Parallel pathways of virus recognition. PubmedID 1...6713969 Title Parallel pathways of virus recognition. Authors Tenoever BR, Maniatis T. Publication Immunity.

  10. DMPD: Regulation of mitochondrial antiviral signaling pathways. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18549796 Regulation of mitochondrial antiviral signaling pathways. Moore CB, Ting J...P. Immunity. 2008 Jun;28(6):735-9. (.png) (.svg) (.html) (.csml) Show Regulation of mitochondrial antiviral ...signaling pathways. PubmedID 18549796 Title Regulation of mitochondrial antiviral signaling pathways. Author

  11. DMPD: Signaling pathways activated by microorganisms. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17303405 Signaling pathways activated by microorganisms. Takeuchi O, Akira S. Curr ...Opin Cell Biol. 2007 Apr;19(2):185-91. Epub 2007 Feb 15. (.png) (.svg) (.html) (.csml) Show Signaling pathwa...ys activated by microorganisms. PubmedID 17303405 Title Signaling pathways activated by microorganisms. Auth

  12. DMPD: All is not Toll: new pathways in DNA recognition. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 16446382 All is not Toll: new pathways in DNA recognition. Wagner H, Bauer S. J Exp... Med. 2006 Feb 20;203(2):265-8. Epub 2006 Jan 30. (.png) (.svg) (.html) (.csml) Show All is not Toll: new pa...thways in DNA recognition. PubmedID 16446382 Title All is not Toll: new pathways in DNA recognition. Authors

  13. DMPD: LPS/TLR4 signal transduction pathway. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18304834 LPS/TLR4 signal transduction pathway. Lu YC, Yeh WC, Ohashi PS. Cytokine. ...2008 May;42(2):145-51. Epub 2008 Mar 4. (.png) (.svg) (.html) (.csml) Show LPS/TLR4 signal transduction path...way. PubmedID 18304834 Title LPS/TLR4 signal transduction pathway. Authors Lu YC, Yeh WC, Ohashi PS. Publica

  14. DMPD: Afferent pathways of pyrogen signaling. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 9917870 Afferent pathways of pyrogen signaling. Blatteis CM, Sehic E, Li S. Ann N Y... Acad Sci. 1998 Sep 29;856:95-107. (.png) (.svg) (.html) (.csml) Show Afferent pathways of pyrogen signaling.... PubmedID 9917870 Title Afferent pathways of pyrogen signaling. Authors Blatteis CM, Sehic E, Li S. Publica

  15. DMPD: Signalling pathways mediating type I interferon gene expression. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17904888 Signalling pathways mediating type I interferon gene expression. Edwards M...csml) Show Signalling pathways mediating type I interferon gene expression. PubmedID 17904888 Title Signalli...ng pathways mediating type I interferon gene expression. Authors Edwards MR, Slat

  16. Engineering the spatial organization of metabolic pathways

    DEFF Research Database (Denmark)

    Albertsen, Line; Maury, Jerome; Bach, Lars Stougaard;

    does however often depend on both heterologous and host enzymes. In this case, no spatial coordination of the biosynthetic enzymes can be expected to be in place. Presumably this contributes to the low productivity regularly observed for heterologous pathways. In one test case, we investigated whether...... of the spatial organization of biosynthetic pathways. Several natural systems for ensuring optimal spatial arrangement of biosynthetic enzymes exist. Sequentially acting enzymes can for example be positioned in close proximity by attachment to cellular structures, up-concentration in membrane enclosed organelles......, as enzyme fusion combined with down-regulation of a competing pathway and up-regulation of a selected pathway enzyme resulted in a five-fold higher sesquiterpene production. This simple test case demonstrates that engineering of the spatial organization of pathways has great potential for diverting flux...

  17. Ordering the multiple pathways of apoptosis.

    Science.gov (United States)

    Park, D S; Stefanis, L; Greene, L A

    1997-11-01

    Apoptosis plays an important role in development, homeostasis, and disease. Current work has suggested that apoptosis can be evoked by multiple stimuli that, in turn, initiate distinct death pathways. Recently, exciting advances have been made in the understanding of biochemical pathways that regulate apoptotic processes. These pathways contain both evolutionarily conserved elements and components that are dependent on the death stimulus and cell context. Accordingly, this review focuses on the compositions and relative ordering of the apoptotic pathways in four different death paradigms: activation of receptors of the Fas ligand, destruction by cytotoxic T lymphocytes, exposure to DNA damaging agents, and loss of support by neurotrophic factors. These examples illustrate the conservation and divergence in the ways that death pathways are composed and ordered. (Trends Cardiovasc Med 1997;7:294-301). © 1997, Elsevier Science Inc.

  18. Tapping RNA silencing pathways for plant biotechnology.

    Science.gov (United States)

    Frizzi, Alessandra; Huang, Shihshieh

    2010-08-01

    Plants have evolved a variety of gene silencing pathways mediated by small RNAs. Mostly 21 or 24 nt in size, these small RNAs repress the expression of sequence homologous genes at the transcriptional, post-transcriptional and translational levels. These pathways, also referred as RNA silencing pathways, play important roles in regulating growth and development as well as in response to both biotic and abiotic stress. Although the molecular basis of these complicated and interconnected pathways has become clear only in recent years, RNA silencing effects were observed and utilized in transgenic plants early in the plant biotechnology era, more than two decades ago. Today, with a better understanding of the pathways, various genetic engineering approaches have been developed to apply RNA silencing more effectively and broadly. In addition to summarizing the current models of RNA silencing, this review discusses examples of its potential uses and related issues concerning its application in plant biotechnology.

  19. Pathway projector: web-based zoomable pathway browser using KEGG atlas and Google Maps API.

    Directory of Open Access Journals (Sweden)

    Nobuaki Kono

    Full Text Available BACKGROUND: Biochemical pathways provide an essential context for understanding comprehensive experimental data and the systematic workings of a cell. Therefore, the availability of online pathway browsers will facilitate post-genomic research, just as genome browsers have contributed to genomics. Many pathway maps have been provided online as part of public pathway databases. Most of these maps, however, function as the gateway interface to a specific database, and the comprehensiveness of their represented entities, data mapping capabilities, and user interfaces are not always sufficient for generic usage. METHODOLOGY/PRINCIPAL FINDINGS: We have identified five central requirements for a pathway browser: (1 availability of large integrated maps showing genes, enzymes, and metabolites; (2 comprehensive search features and data access; (3 data mapping for transcriptomic, proteomic, and metabolomic experiments, as well as the ability to edit and annotate pathway maps; (4 easy exchange of pathway data; and (5 intuitive user experience without the requirement for installation and regular maintenance. According to these requirements, we have evaluated existing pathway databases and tools and implemented a web-based pathway browser named Pathway Projector as a solution. CONCLUSIONS/SIGNIFICANCE: Pathway Projector provides integrated pathway maps that are based upon the KEGG Atlas, with the addition of nodes for genes and enzymes, and is implemented as a scalable, zoomable map utilizing the Google Maps API. Users can search pathway-related data using keywords, molecular weights, nucleotide sequences, and amino acid sequences, or as possible routes between compounds. In addition, experimental data from transcriptomic, proteomic, and metabolomic analyses can be readily mapped. Pathway Projector is freely available for academic users at (http://www.g-language.org/PathwayProjector/.

  20. ATPA induced GluR5-containing kainite receptor S-nitrosylation via activation of GluR5-Gq-PLC-IP(3)R pathway and signalling module GluR5·PSD-95·nNOS.

    Science.gov (United States)

    Zhang, Hai-Jian; Li, Chong; Zhang, Guang-Yi

    2012-12-01

    GluR5-containing kainite receptor (GluR5-KAR) plays an important role in the pathophysiology of nervous system diseases, while S-nitrosylation exerts a variety of effects on biological systems. However, the mechanism of GluR5-KAR S-nitrosylation is still unclear up to now. Here our researches found that GluR5-KAR selective agonist ATPA stimulation activated the nonclassical GluR5-KAR-Gq-PLC-IP(3)R pathway and the signalling module GluR5·PSD-95·nNOS (the former is more important), led to Ca(2+) release from intracellular calcium stores endoplasmic reticulum (ER) to cytoplasm and extracellular calcium indrawal, respectively, which further resulted in nNOS activation and GluR5-KAR S-nitrosylation, and then inhibited GluR5-mediated whole-cell current attenuation and induced apoptosis in primary cultured hippocampal neurons. Clarification of the primary mechanisms of GluR5-KAR S-nitrosylation induced by ATPA and identification of critical cysteine for GluR5-2a S-nitrosylation (Cys231 and Cys804) open up a brand-new field for revealing downstream signalling pathway of GluR5-KAR and its molecular characteristics, exploring the pathogenesis of neurological diseases and searching for promising therapies.

  1. Novel personalized pathway-based metabolomics models reveal key metabolic pathways for breast cancer diagnosis

    DEFF Research Database (Denmark)

    Huang, Sijia; Chong, Nicole; Lewis, Nathan

    2016-01-01

    . Methods: We propose that higher-order functional representation of metabolomics data, such as pathway-based metabolomic features, can be used as robust biomarkers for breast cancer. Towards this, we have developed a new computational method that uses personalized pathway dysregulation scores for disease...... the Curve, a receiver operating characteristic curve) of 0.968 and 0.934, sensitivities of 0.946 and 0.954, and specificities of 0.934 and 0.918. These two metabolomics-based pathway models are further validated by RNA-Seq-based TCGA (The Cancer Genome Atlas) breast cancer data, with AUCs of 0.995 and 0.......993. Moreover, important metabolic pathways, such as taurine and hypotaurine metabolism and the alanine, aspartate, and glutamate pathway, are revealed as critical biological pathways for early diagnosis of breast cancer. Conclusions: We have successfully developed a new type of pathway-based model to study...

  2. Remodeling the isoprenoid pathway in tobacco by expressing the cytoplasmic mevalonate pathway in chloroplasts.

    Science.gov (United States)

    Kumar, Shashi; Hahn, Frederick M; Baidoo, Edward; Kahlon, Talwinder S; Wood, Delilah F; McMahan, Colleen M; Cornish, Katrina; Keasling, Jay D; Daniell, Henry; Whalen, Maureen C

    2012-01-01

    Metabolic engineering to enhance production of isoprenoid metabolites for industrial and medical purposes is an important goal. The substrate for isoprenoid synthesis in plants is produced by the mevalonate pathway (MEV) in the cytosol and by the 2-C-methyl-d-erythritol 4-phosphate (MEP) pathway in plastids. A multi-gene approach was employed to insert the entire cytosolic MEV pathway into the tobacco chloroplast genome. Molecular analysis confirmed the site-specific insertion of seven transgenes and homoplasmy. Functionality was demonstrated by unimpeded growth on fosmidomycin, which specifically inhibits the MEP pathway. Transplastomic plants containing the MEV pathway genes accumulated higher levels of mevalonate, carotenoids, squalene, sterols, and triacyglycerols than control plants. This is the first time an entire eukaryotic pathway with six enzymes has been transplastomically expressed in plants. Thus, we have developed an important tool to redirect metabolic fluxes in the isoprenoid biosynthesis pathway and a viable multigene strategy for engineering metabolism in plants.

  3. A markov classification model for metabolic pathways

    Directory of Open Access Journals (Sweden)

    Mamitsuka Hiroshi

    2010-01-01

    Full Text Available Abstract Background This paper considers the problem of identifying pathways through metabolic networks that relate to a specific biological response. Our proposed model, HME3M, first identifies frequently traversed network paths using a Markov mixture model. Then by employing a hierarchical mixture of experts, separate classifiers are built using information specific to each path and combined into an ensemble prediction for the response. Results We compared the performance of HME3M with logistic regression and support vector machines (SVM for both simulated pathways and on two metabolic networks, glycolysis and the pentose phosphate pathway for Arabidopsis thaliana. We use AltGenExpress microarray data and focus on the pathway differences in the developmental stages and stress responses of Arabidopsis. The results clearly show that HME3M outperformed the comparison methods in the presence of increasing network complexity and pathway noise. Furthermore an analysis of the paths identified by HME3M for each metabolic network confirmed known biological responses of Arabidopsis. Conclusions This paper clearly shows HME3M to be an accurate and robust method for classifying metabolic pathways. HME3M is shown to outperform all comparison methods and further is capable of identifying known biologically active pathways within microarray data.

  4. Targeting the TGFβ pathway for cancer therapy.

    Science.gov (United States)

    Neuzillet, Cindy; Tijeras-Raballand, Annemilaï; Cohen, Romain; Cros, Jérôme; Faivre, Sandrine; Raymond, Eric; de Gramont, Armand

    2015-03-01

    The TGFβ signaling pathway has pleiotropic functions regulating cell growth, differentiation, apoptosis, motility and invasion, extracellular matrix production, angiogenesis, and immune response. TGFβ signaling deregulation is frequent in tumors and has crucial roles in tumor initiation, development and metastasis. TGFβ signaling inhibition is an emerging strategy for cancer therapy. The role of the TGFβ pathway as a tumor-promoter or suppressor at the cancer cell level is still a matter of debate, due to its differential effects at the early and late stages of carcinogenesis. In contrast, at the microenvironment level, the TGFβ pathway contributes to generate a favorable microenvironment for tumor growth and metastasis throughout all the steps of carcinogenesis. Then, targeting the TGFβ pathway in cancer may be considered primarily as a microenvironment-targeted strategy. In this review, we focus on the TGFβ pathway as a target for cancer therapy. In the first part, we provide a comprehensive overview of the roles played by this pathway and its deregulation in cancer, at the cancer cell and microenvironment levels. We go on to describe the preclinical and clinical results of pharmacological strategies to target the TGFβ pathway, with a highlight on the effects on tumor microenvironment. We then explore the perspectives to optimize TGFβ inhibition therapy in different tumor settings.

  5. Driving and dementia: a clinical decision pathway

    Science.gov (United States)

    Carter, Kirsty; Monaghan, Sophie; O'Brien, John; Teodorczuk, Andrew; Mosimann, Urs; Taylor, John-Paul

    2015-01-01

    Objective This study aimed to develop a pathway to bring together current UK legislation, good clinical practice and appropriate management strategies that could be applied across a range of healthcare settings. Methods The pathway was constructed by a multidisciplinary clinical team based in a busy Memory Assessment Service. A process of successive iteration was used to develop the pathway, with input and refinement provided via survey and small group meetings with individuals from a wide range of regional clinical networks and diverse clinical backgrounds as well as discussion with mobility centres and Forum of Mobility Centres, UK. Results We present a succinct clinical pathway for patients with dementia, which provides a decision-making framework for how health professionals across a range of disciplines deal with patients with dementia who drive. Conclusions By integrating the latest guidance from diverse roles within older people's health services and key experts in the field, the resulting pathway reflects up-to-date policy and encompasses differing perspectives and good practice. It is potentially a generalisable pathway that can be easily adaptable for use internationally, by replacing UK legislation for local regulations. A limitation of this pathway is that it does not address the concern of mild cognitive impairment and how this condition relates to driving safety. © 2014 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons, Ltd. PMID:24865643

  6. Logical modelling of Drosophila signalling pathways.

    Science.gov (United States)

    Mbodj, Abibatou; Junion, Guillaume; Brun, Christine; Furlong, Eileen E M; Thieffry, Denis

    2013-09-01

    A limited number of signalling pathways are involved in the specification of cell fate during the development of all animals. Several of these pathways were originally identified in Drosophila. To clarify their roles, and possible cross-talk, we have built a logical model for the nine key signalling pathways recurrently used in metazoan development. In each case, we considered the associated ligands, receptors, signal transducers, modulators, and transcription factors reported in the literature. Implemented using the logical modelling software GINsim, the resulting models qualitatively recapitulate the main characteristics of each pathway, in wild type as well as in various mutant situations (e.g. loss-of-function or gain-of-function). These models constitute pluggable modules that can be used to assemble comprehensive models of complex developmental processes. Moreover, these models of Drosophila pathways could serve as scaffolds for more complicated models of orthologous mammalian pathways. Comprehensive model annotations and GINsim files are provided for each of the nine considered pathways.

  7. Dissecting the PCP pathway: one or more pathways?: Does a separate Wnt-Fz-Rho pathway drive morphogenesis?

    Science.gov (United States)

    Lapébie, Pascal; Borchiellini, Carole; Houliston, Evelyn

    2011-10-01

    Planar cell polarity (PCP), the alignment of cells within 2D tissue planes, involves a set of core molecular regulators highly conserved between animals and cell types. These include the transmembrane proteins Frizzled (Fz) and VanGogh and the cytoplasmic regulators Dishevelled (Dsh) and Prickle. It is widely accepted that this core forms part of a 'PCP pathway' for signal transduction, which can affect cell morphology through activation of an evolutionary ancient regulatory module involving Rho family GTPases and Myosin II, and/or the JNK kinase cascade. We have re-examined the evidence for interactions between the proposed PCP pathway components, and question the placing of the cell morphology regulators in the same pathway as the PCP core. While Fz and Dsh are clearly involved in both PCP and Rho-based cell morphology regulation, available evidence cannot currently discriminate whether these processes are linked mechanistically by a shared Fz/Dsh population, or pass by two distinct pathways.

  8. Role of care pathways in interprofessional teamwork.

    Science.gov (United States)

    Scaria, Minimol Kulakkottu

    2016-08-24

    Cohesive interprofessional teamwork is essential to successful healthcare services. Interprofessional teamwork is the means by which different healthcare professionals - with diverse knowledge, skills and talents - collaborate to achieve a common goal. Several interventions are available to improve teamwork in the healthcare setting. This article explores the role of care pathways in improving interprofessional teamwork. Care pathways enhance teamwork by promoting coordination, collaboration, communication and decision making to achieve optimal healthcare outcomes. They result in improved staff knowledge, communication, documentation and interprofessional relations. Care pathways also contribute to patient-centred care and increase patient satisfaction.

  9. Syngas Upgrading to Hydrocarbon Fuels Technology Pathway

    Energy Technology Data Exchange (ETDEWEB)

    Talmadge, M.; Biddy, M.; Dutta, A.; Jones, S.; Meyer, A.

    2013-03-01

    This technology pathway case investigates the upgrading of woody biomass derived synthesis gas (syngas) to hydrocarbon biofuels. While this specific discussion focuses on the conversion of syngas via a methanol intermediate to hydrocarbon blendstocks, there are a number of alternative conversion routes for production of hydrocarbons through a wide array of intermediates from syngas. Future work will also consider the variations to this pathway to determine the most economically viable and lowest risk conversion route. Technical barriers and key research needs have been identified that should be pursued for the syngas-to-hydrocarbon pathway to be competitive with petroleum-derived gasoline-, diesel- and jet-range hydrocarbon blendstocks.

  10. Cancer and deregulation of stem cells pathways

    Directory of Open Access Journals (Sweden)

    Filipe Correia Martins

    2011-12-01

    Full Text Available Stem cells may have an important etiological role in cancer. Their classic regulatory pathways are deregulated in tumors, strengthening the stem cell theory of cancer. In this manuscript, we review Wnt, Notch and Hedhehog pathways, describing which of their factors may be responsible for the neoplastic development. Furthermore, we classify these elements as oncogenes or tumor suppressor genes, demonstrating their mutation implications in cancer. The activation of these pathways is associated with the expression of certain genes which maintain proliferation and apoptosis inhibition. Further work should be carried out in the future in order to control tumor development by controlling these signaling cascades.

  11. New pathway for the metabolism of pentitols

    Science.gov (United States)

    London, Jack; Chace, Nina M.

    1977-01-01

    Certain strains of Lactobacillus casei can grow at the expense of one or more pentitols. These microorganisms possess a pentitol phosphate pathway that appears to be analogous to the hexitol phosphate pathway found in many facultatively anaerobic bacteria. Pentitol is transported into the cell by a phospho enolpyruvate phosphotransferase system that converts it to pentitol phosphate, whereupon a specific dehydrogenase oxidizes the intermediate product to ketopentose phosphate. The ketopentose phosphate is subsequently converted to xylulose-5-P and enters one of the pathways of central metabolism. Images PMID:16592445

  12. Amygdalar vocalization pathways in the squirrel monkey.

    Science.gov (United States)

    Jürgens, U

    1982-06-10

    In 22 squirrel monkeys (Saimiri sciureus) vocalization-eliciting electrodes were implanted into the amygdala and along the trajectory of the stria terminalis. Then, lesions were placed in the stria terminalis, its bed nucleus, the ventral amygdalofugal pathway and several di- and mesencephalic structures in order to find out the pathways along which the amygdala exerts its vocalization-controlling influence. It was found that different call types are controlled by different pathways. Purring and chattering calls, which express a self-confident, challenging attitude and an attempt to recruit fellow-combatants in intra-specific mobbing, respectively, are controlled via the stria terminalis; alarm peep and groaning calls, in contrast, which indicate flight motivation and resentment, respectively, are triggered via the ventral amygdalofugal fibre bundle. Both pathways traverse the dorsolateral and dorsomedial hypothalamus, respectively, and unite in the periaqueductal grey of the midbrain.

  13. The Pentose Phosphate Pathway in Parasitic Trypanosomatids.

    Science.gov (United States)

    Kovářová, Julie; Barrett, Michael P

    2016-08-01

    Parasitic trypanosomatids cause important diseases. Dissecting the biochemistry of these organisms offers a means of discovering targets against which inhibitors may be designed and developed as drugs. The pentose phosphate pathway is a key route of glucose metabolism in most organisms, providing NADPH for use as a cellular reductant and various carbohydrate intermediates used in cellular metabolism. The pathway and its enzymes have been studied in Trypanosoma brucei, Trypanosoma cruzi, and various Leishmania species. Its functions in these parasites are becoming clear. Some enzymes of the pathway are essential to the parasites and have structural features distinguishing them from their mammalian counterparts, and this has stimulated several programs of inhibitor discovery with a view to targeting the pathway with new drugs.

  14. The Wnt signaling pathway in cancer.

    Science.gov (United States)

    Duchartre, Yann; Kim, Yong-Mi; Kahn, Michael

    2016-03-01

    The Wnt signaling pathway is critically involved in both the development and homeostasis of tissues via regulation of their endogenous stem cells. Aberrant Wnt signaling has been described as a key player in the initiation of and/or maintenance and development of many cancers, via affecting the behavior of Cancer Stem Cells (CSCs). CSCs are considered by most to be responsible for establishment of the tumor and also for disease relapse, as they possess inherent drug-resistance properties. The development of new therapeutic compounds targeting the Wnt signaling pathway promises new hope to eliminate CSCs and achieve cancer eradication. However, a major challenge resides in developing a strategy efficient enough to target the dysregulated Wnt pathway in CSCs, while being safe enough to not damage the normal somatic stem cell population required for tissue homeostasis and repair. Here we review recent therapeutic approaches to target the Wnt pathway and their clinical applications.

  15. Clinical implications of hedgehog signaling pathway inhibitors

    Institute of Scientific and Technical Information of China (English)

    Hailan Liu; Dongsheng Gu; Jingwu Xie

    2011-01-01

    Hedgehog was first described in Drosophila melanogaster by the Nobel laureates Eric Wieschaus and Christiane Nusslein-Volhard. The hedgehog (Hh) pathway is a major regulator of cell differentiation,proliferation, tissue polarity, stem cell maintenance, and carcinogenesis. The first link of Hh signaling to cancer was established through studies of a rare familial disease, Gorlin syndrome, in 1996. Follow-up studies revealed activation of this pathway in basal cell carcinoma, medulloblastoma and, leukemia as well as in gastrointestinal, lung, ovarian, breast, and prostate cancer. Targeted inhibition of Hh signaling is now believed to be effective in the treatment and prevention of human cancer. The discovery and synthesis of specific inhibitors for this pathway are even more exciting. In this review, we summarize major advances in the understanding of Hh signaling pathway activation in human cancer, mouse models for studying Hhmediated carcinogenesis, the roles of Hh signaling in tumor development and metastasis, antagonists for Hh signaling and their clinical implications.

  16. Imaging the Visual Pathway in Neuromyelitis Optica

    Directory of Open Access Journals (Sweden)

    Caspar F. Pfueller

    2011-01-01

    Full Text Available The focus of this paper is to summarize the current knowledge on visual pathway damage in neuromyelitis optica (NMO assessed by magnetic resonance imaging (MRI and optical coherence tomography (OCT.

  17. Imaging the visual pathway in neuromyelitis optica

    OpenAIRE

    Pfueller, Caspar F.; Friedemann Paul

    2011-01-01

    The focus of this paper is to summarize the current knowledge on visual pathway damage in neuromyelitis optica (NMO) assessed by magnetic resonance imaging (MRI) and optical coherence tomography (OCT).

  18. Genetic dissection of cardiac growth control pathways

    Science.gov (United States)

    MacLellan, W. R.; Schneider, M. D.

    2000-01-01

    Cardiac muscle cells exhibit two related but distinct modes of growth that are highly regulated during development and disease. Cardiac myocytes rapidly proliferate during fetal life but exit the cell cycle irreversibly soon after birth, following which the predominant form of growth shifts from hyperplastic to hypertrophic. Much research has focused on identifying the candidate mitogens, hypertrophic agonists, and signaling pathways that mediate these processes in isolated cells. What drives the proliferative growth of embryonic myocardium in vivo and the mechanisms by which adult cardiac myocytes hypertrophy in vivo are less clear. Efforts to answer these questions have benefited from rapid progress made in techniques to manipulate the murine genome. Complementary technologies for gain- and loss-of-function now permit a mutational analysis of these growth control pathways in vivo in the intact heart. These studies have confirmed the importance of suspected pathways, have implicated unexpected pathways as well, and have led to new paradigms for the control of cardiac growth.

  19. The Notch pathway in colorectal cancer.

    Science.gov (United States)

    Vinson, Kaitlyn E; George, Dennis C; Fender, Alexander W; Bertrand, Fred E; Sigounas, George

    2016-04-15

    Colorectal cancer (CRC) is the third leading cause of cancer death worldwide. It is also the third most common cancer diagnosis among men, and the second most common cancer diagnosis among women. Globally, CRC can account for nearly 694,000 annual deaths. It is widely appreciated that CRC is the result of dysregulated cellular pathways that promote an inappropriate stem-cell-like phenotype, apoptotic resistance, unchecked proliferation and metastatic spread. While no single pathway is responsible for all of these attributes, an array of recent studies suggests a pivotal role for abnormal Notch-1 signaling in CRC, in part due to interconnectivity of Notch with other pathways. This review will summarize recent evidence for a role of Notch signaling in CRC, will consider interconnectivity between Notch and other pathways involved in CRC and will discuss the possible utility of targeting Notch as a CRC therapeutic.

  20. Salicylic acid-independent plant defence pathways

    OpenAIRE

    Pieterse, C.M.J.; Loon, L. C. Van

    1999-01-01

    Salicylic acid is an important signalling molecule involved in both locally and systemically induced disease resistance responses. Recent advances in our understanding of plant defence signalling have revealed that plants employ a network of signal transduction pathways, some of which are independent of salicylic acid. Evidence is emerging that jasmonic acid and ethylene play key roles in these salicylic acid-independent pathways. Cross-talk between the salicylic acid-dependent and the salicy...

  1. Pathway Model and Nonextensive Statistical Mechanics

    Science.gov (United States)

    Mathai, A. M.; Haubold, H. J.; Tsallis, C.

    2015-12-01

    The established technique of eliminating upper or lower parameters in a general hypergeometric series is profitably exploited to create pathways among confluent hypergeometric functions, binomial functions, Bessel functions, and exponential series. One such pathway, from the mathematical statistics point of view, results in distributions which naturally emerge within nonextensive statistical mechanics and Beck-Cohen superstatistics, as pursued in generalizations of Boltzmann-Gibbs statistics.

  2. The mevalonate pathway in C. Elegans

    Directory of Open Access Journals (Sweden)

    Rauthan Manish

    2011-12-01

    Full Text Available Abstract The mevalonate pathway in human is responsible for the synthesis of cholesterol and other important biomolecules such as coenzyme Q, dolichols and isoprenoids. These molecules are required in the cell for functions ranging from signaling to membrane integrity, protein prenylation and glycosylation, and energy homeostasis. The pathway consists of a main trunk followed by sub-branches that synthesize the different biomolecules. The majority of our knowledge about the mevalonate pathway is currently focused on the cholesterol synthesis branch, which is the target of the cholesterol-lowering statins; less is known about the function and regulation of the non-cholesterol-related branches. To study them, we need a biological system where it is possible to specifically modulate these metabolic branches individually or in groups. The nematode Caenorhabditis elegans (C. elegans is a promising model to study these non-cholesterol branches since its mevalonate pathway seems very well conserved with that in human except that it has no cholesterol synthesis branch. The simple genetic makeup and tractability of C. elegans makes it relatively easy to identify and manipulate key genetic components of the mevalonate pathway, and to evaluate the consequences of tampering with their activity. This general experimental approach should lead to new insights into the physiological roles of the non-cholesterol part of the mevalonate pathway. This review will focus on the current knowledge related to the mevalonate pathway in C. elegans and its possible applications as a model organism to study the non-cholesterol functions of this pathway.

  3. Genes and (common pathways underlying drug addiction.

    Directory of Open Access Journals (Sweden)

    Chuan-Yun Li

    2008-01-01

    Full Text Available Drug addiction is a serious worldwide problem with strong genetic and environmental influences. Different technologies have revealed a variety of genes and pathways underlying addiction; however, each individual technology can be biased and incomplete. We integrated 2,343 items of evidence from peer-reviewed publications between 1976 and 2006 linking genes and chromosome regions to addiction by single-gene strategies, microrray, proteomics, or genetic studies. We identified 1,500 human addiction-related genes and developed KARG (http://karg.cbi.pku.edu.cn, the first molecular database for addiction-related genes with extensive annotations and a friendly Web interface. We then performed a meta-analysis of 396 genes that were supported by two or more independent items of evidence to identify 18 molecular pathways that were statistically significantly enriched, covering both upstream signaling events and downstream effects. Five molecular pathways significantly enriched for all four different types of addictive drugs were identified as common pathways which may underlie shared rewarding and addictive actions, including two new ones, GnRH signaling pathway and gap junction. We connected the common pathways into a hypothetical common molecular network for addiction. We observed that fast and slow positive feedback loops were interlinked through CAMKII, which may provide clues to explain some of the irreversible features of addiction.

  4. Pathway and Enzyme Redundancy in Putrescine Catabolism in Escherichia coli

    OpenAIRE

    Schneider, Barbara L.; Reitzer, Larry

    2012-01-01

    Putrescine as the sole carbon source requires a novel catabolic pathway with glutamylated intermediates. Nitrogen limitation does not induce genes of this glutamylated putrescine (GP) pathway but instead induces genes for a putrescine catabolic pathway that starts with a transaminase-dependent deamination. We determined pathway utilization with putrescine as the sole nitrogen source by examining mutants with defects in both pathways. Blocks in both the GP and transaminase pathways were requir...

  5. Subpathway Analysis based on Signaling-Pathway Impact Analysis of Signaling Pathway.

    Directory of Open Access Journals (Sweden)

    Xianbin Li

    Full Text Available Pathway analysis is a common approach to gain insight from biological experiments. Signaling-pathway impact analysis (SPIA is one such method and combines both the classical enrichment analysis and the actual perturbation on a given pathway. Because this method focuses on a single pathway, its resolution generally is not very high because the differentially expressed genes may be enriched in a local region of the pathway. In the present work, to identify cancer-related pathways, we incorporated a recent subpathway analysis method into the SPIA method to form the "sub-SPIA method." The original subpathway analysis uses the k-clique structure to define a subpathway. However, it is not sufficiently flexible to capture subpathways with complex structure and usually results in many overlapping subpathways. We therefore propose using the minimal-spanning-tree structure to find a subpathway. We apply this approach to colorectal cancer and lung cancer datasets, and our results show that sub-SPIA can identify many significant pathways associated with each specific cancer that other methods miss. Based on the entire pathway network in the Kyoto Encyclopedia of Genes and Genomes, we find that the pathways identified by sub-SPIA not only have the largest average degree, but also are more closely connected than those identified by other methods. This result suggests that the abnormality signal propagating through them might be responsible for the specific cancer or disease.

  6. Neural pathways for visual speech perception

    Directory of Open Access Journals (Sweden)

    Lynne E Bernstein

    2014-12-01

    Full Text Available This paper examines the questions, what levels of speech can be perceived visually, and how is visual speech represented by the brain? Review of the literature leads to the conclusions that every level of psycholinguistic speech structure (i.e., phonetic features, phonemes, syllables, words, and prosody can be perceived visually, although individuals differ in their abilities to do so; and that there are visual modality-specific representations of speech qua speech in higher-level vision brain areas. That is, the visual system represents the modal patterns of visual speech. The suggestion that the auditory speech pathway receives and represents visual speech is examined in light of neuroimaging evidence on the auditory speech pathways. We outline the generally agreed-upon organization of the visual ventral and dorsal pathways and examine several types of visual processing that might be related to speech through those pathways, specifically, face and body, orthography, and sign language processing. In this context, we examine the visual speech processing literature, which reveals widespread diverse patterns activity in posterior temporal cortices in response to visual speech stimuli. We outline a model of the visual and auditory speech pathways and make several suggestions: (1 The visual perception of speech relies on visual pathway representations of speech qua speech. (2 A proposed site of these representations, the temporal visual speech area (TVSA has been demonstrated in posterior temporal cortex, ventral and posterior to multisensory posterior superior temporal sulcus (pSTS. (3 Given that visual speech has dynamic and configural features, its representations in feedforward visual pathways are expected to integrate these features, possibly in TVSA.

  7. Neural pathways for visual speech perception.

    Science.gov (United States)

    Bernstein, Lynne E; Liebenthal, Einat

    2014-01-01

    This paper examines the questions, what levels of speech can be perceived visually, and how is visual speech represented by the brain? Review of the literature leads to the conclusions that every level of psycholinguistic speech structure (i.e., phonetic features, phonemes, syllables, words, and prosody) can be perceived visually, although individuals differ in their abilities to do so; and that there are visual modality-specific representations of speech qua speech in higher-level vision brain areas. That is, the visual system represents the modal patterns of visual speech. The suggestion that the auditory speech pathway receives and represents visual speech is examined in light of neuroimaging evidence on the auditory speech pathways. We outline the generally agreed-upon organization of the visual ventral and dorsal pathways and examine several types of visual processing that might be related to speech through those pathways, specifically, face and body, orthography, and sign language processing. In this context, we examine the visual speech processing literature, which reveals widespread diverse patterns of activity in posterior temporal cortices in response to visual speech stimuli. We outline a model of the visual and auditory speech pathways and make several suggestions: (1) The visual perception of speech relies on visual pathway representations of speech qua speech. (2) A proposed site of these representations, the temporal visual speech area (TVSA) has been demonstrated in posterior temporal cortex, ventral and posterior to multisensory posterior superior temporal sulcus (pSTS). (3) Given that visual speech has dynamic and configural features, its representations in feedforward visual pathways are expected to integrate these features, possibly in TVSA.

  8. Bacterial variations on the methionine salvage pathway

    Directory of Open Access Journals (Sweden)

    Haas Dieter

    2004-03-01

    Full Text Available Abstract Background The thiomethyl group of S-adenosylmethionine is often recycled as methionine from methylthioadenosine. The corresponding pathway has been unravelled in Bacillus subtilis. However methylthioadenosine is subjected to alternative degradative pathways depending on the organism. Results This work uses genome in silico analysis to propose methionine salvage pathways for Klebsiella pneumoniae, Leptospira interrogans, Thermoanaerobacter tengcongensis and Xylella fastidiosa. Experiments performed with mutants of B. subtilis and Pseudomonas aeruginosa substantiate the hypotheses proposed. The enzymes that catalyze the reactions are recruited from a variety of origins. The first, ubiquitous, enzyme of the pathway, MtnA (methylthioribose-1-phosphate isomerase, belongs to a family of proteins related to eukaryotic intiation factor 2B alpha. mtnB codes for a methylthioribulose-1-phosphate dehydratase. Two reactions follow, that of an enolase and that of a phosphatase. While in B. subtilis this is performed by two distinct polypeptides, in the other organisms analyzed here an enolase-phosphatase yields 1,2-dihydroxy-3-keto-5-methylthiopentene. In the presence of dioxygen an aci-reductone dioxygenase yields the immediate precursor of methionine, ketomethylthiobutyrate. Under some conditions this enzyme produces carbon monoxide in B. subtilis, suggesting a route for a new gaseous mediator in bacteria. Ketomethylthiobutyrate is finally transaminated by an aminotransferase that exists usually as a broad specificity enzyme (often able to transaminate aromatic aminoacid keto-acid precursors or histidinol-phosphate. Conclusion A functional methionine salvage pathway was experimentally demonstrated, for the first time, in P. aeruginosa. Apparently, methionine salvage pathways are frequent in Bacteria (and in Eukarya, with recruitment of different polypeptides to perform the needed reactions (an ancestor of a translation initiation factor and Ru

  9. JNK pathway in osteosarcoma: pathogenesis and therapeutics.

    Science.gov (United States)

    Li, Yu-Sheng; Deng, Zhen-Han; Zeng, Chao; Lei, Guang-Hua

    2016-10-01

    The c-Jun NH2-terminal kinase (JNK) is a member of the mitogen-activated protein kinase super family. JNK can phosphorylate a number of activator protein-1 components, activating several transcription factors, and thus, JNK signaling pathway is being involved in several carcinogenic mechanisms. In this study, we have reviewed the recent updates of the association of JNK pathway with osteosarcoma (OS), which is one of the most common and aggressive bone malignancies. In this review, we have explored the databases like PubMed, Google Scholar, MEDLINE, etc., and collected the most relevant papers of JNK signaling pathway involved in the pathogenesis and therapeutics of OS. Evidence showed that JNK is a master protein kinase that plays an important role in osteoblast proliferation, differentiation and apoptosis. Interesting reports showed that chemical JNK inhibitors reduce OS cell proliferation and metastasis. Many of the components of this pathway have now been identified and the application of JNK inhibitors has been proven to work in vivo in human and in animal models; however, JNK pathway has not been translated into clinical use. Therapeutic interventions of potent and selective inhibitors of JNK might provide promising therapeutic approaches for the treatment of OS, and could improve the survival rate and quality of life of OS patients.

  10. Persisting eicosanoid pathways in rheumatic diseases.

    Science.gov (United States)

    Korotkova, Marina; Jakobsson, Per-Johan

    2014-04-01

    An unmet clinical need exists for early treatment of rheumatic diseases and improved treatment strategies that can better maintain remission with reduced ongoing subclinical inflammation and bone destruction. Eicosanoids form one of the most complex networks in the body controlling many physiological and pathophysiological processes, including inflammation, autoimmunity and cancer. Persisting eicosanoid pathways are thought to be involved in the development of rheumatic diseases, and targeting this pathway might enable improved treatment strategies. Several enzymes of the arachidonic acid cascade as well as eicosanoid receptors (all part of the eicosanoid pathway) are today well-recognized targets for anti-inflammatory drugs that can reduce symptoms of inflammation in rheumatic diseases. In this Review, we outline the evidence supporting pivotal roles of eicosanoid signalling in the pathogenesis of rheumatic diseases and discuss findings from studies in animals and humans. We focus first on rheumatoid arthritis and discuss the upregulation of the cyclooxygenase and lipoxygenase pathways as most data are available in this condition. Research into the roles of eicosanoids in other rheumatic diseases (osteoarthritis, idiopathic inflammatory myopathies, systemic lupus erythematosus and gout) is also progressing rapidly and is discussed. Finally, we summarize the prospects of targeting eicosanoid pathways as anti-inflammatory treatment strategies for patients with rheumatic diseases.

  11. Leptin signalling pathways in hypothalamic neurons.

    Science.gov (United States)

    Kwon, Obin; Kim, Ki Woo; Kim, Min-Seon

    2016-04-01

    Leptin is the most critical hormone in the homeostatic regulation of energy balance among those so far discovered. Leptin primarily acts on the neurons of the mediobasal part of hypothalamus to regulate food intake, thermogenesis, and the blood glucose level. In the hypothalamic neurons, leptin binding to the long form leptin receptors on the plasma membrane initiates multiple signaling cascades. The signaling pathways known to mediate the actions of leptin include JAK-STAT signaling, PI3K-Akt-FoxO1 signaling, SHP2-ERK signaling, AMPK signaling, and mTOR-S6K signaling. Recent evidence suggests that leptin signaling in hypothalamic neurons is also linked to primary cilia function. On the other hand, signaling molecules/pathways mitigating leptin actions in hypothalamic neurons have been extensively investigated in an effort to treat leptin resistance observed in obesity. These include SOCS3, tyrosine phosphatase PTP1B, and inflammatory signaling pathways such as IKK-NFκB and JNK signaling, and ER stress-mitochondrial signaling. In this review, we discuss leptin signaling pathways in the hypothalamus, with a particular focus on the most recently discovered pathways.

  12. Signaling Pathways in Cardiac Myocyte Apoptosis

    Science.gov (United States)

    Xia, Peng; Liu, Yuening

    2016-01-01

    Cardiovascular diseases, the number 1 cause of death worldwide, are frequently associated with apoptotic death of cardiac myocytes. Since cardiomyocyte apoptosis is a highly regulated process, pharmacological intervention of apoptosis pathways may represent a promising therapeutic strategy for a number of cardiovascular diseases and disorders including myocardial infarction, ischemia/reperfusion injury, chemotherapy cardiotoxicity, and end-stage heart failure. Despite rapid growth of our knowledge in apoptosis signaling pathways, a clinically applicable treatment targeting this cellular process is currently unavailable. To help identify potential innovative directions for future research, it is necessary to have a full understanding of the apoptotic pathways currently known to be functional in cardiac myocytes. Here, we summarize recent progress in the regulation of cardiomyocyte apoptosis by multiple signaling molecules and pathways, with a focus on the involvement of these pathways in the pathogenesis of heart disease. In addition, we provide an update regarding bench to bedside translation of this knowledge and discuss unanswered questions that need further investigation. PMID:28101515

  13. Molecular pathways: translational and therapeutic implications of the Notch signaling pathway in cancer.

    Science.gov (United States)

    Previs, Rebecca A; Coleman, Robert L; Harris, Adrian L; Sood, Anil K

    2015-03-01

    Over 100 years have passed since the first observation of the notched wing phenotype in Drosophila melanogaster, and significant progress has been made to characterize the role of the Notch receptor, its ligands, downstream targets, and cross-talk with other signaling pathways. The canonical Notch pathway with four Notch receptors (Notch1-4) and five ligands (DLL1, 3-4, Jagged 1-2) is an evolutionarily conserved cell signaling pathway that plays critical roles in cell-fate determination, differentiation, development, tissue patterning, cell proliferation, and death. In cancer, these roles have a critical impact on tumor behavior and response to therapy. Because the role of Notch remains tissue and context dependent, alterations within this pathway may lead to tumor suppressive or oncogenic phenotypes. Although no FDA-approved therapies currently exist for the Notch pathway, multiple therapeutics (e.g., demcizumab, tarextumab, GSI MK-0752, R04929097, and PF63084014) have been developed to target different aspects of this pathway for both hematologic and solid malignancies. Understanding the context-specific effects of the Notch pathway will be important for individualized therapies targeting this pathway.

  14. Genome-Wide Pathway Analysis Identifies Genetic Pathways Associated with Psoriasis.

    Science.gov (United States)

    Aterido, Adrià; Julià, Antonio; Ferrándiz, Carlos; Puig, Lluís; Fonseca, Eduardo; Fernández-López, Emilia; Dauden, Esteban; Sánchez-Carazo, José Luís; López-Estebaranz, José Luís; Moreno-Ramírez, David; Vanaclocha, Francisco; Herrera, Enrique; de la Cueva, Pablo; Dand, Nick; Palau, Núria; Alonso, Arnald; López-Lasanta, María; Tortosa, Raül; García-Montero, Andrés; Codó, Laia; Gelpí, Josep Lluís; Bertranpetit, Jaume; Absher, Devin; Capon, Francesca; Myers, Richard M; Barker, Jonathan N; Marsal, Sara

    2016-03-01

    Psoriasis is a chronic inflammatory disease with a complex genetic architecture. To date, the psoriasis heritability is only partially explained. However, there is increasing evidence that the missing heritability in psoriasis could be explained by multiple genetic variants of low effect size from common genetic pathways. The objective of this study was to identify new genetic variation associated with psoriasis risk at the pathway level. We genotyped 598,258 single nucleotide polymorphisms in a discovery cohort of 2,281 case-control individuals from Spain. We performed a genome-wide pathway analysis using 1,053 reference biological pathways. A total of 14 genetic pathways (PFDR ≤ 2.55 × 10(-2)) were found to be significantly associated with psoriasis risk. Using an independent validation cohort of 7,353 individuals from the UK, a total of 6 genetic pathways were significantly replicated (PFDR ≤ 3.46 × 10(-2)). We found genetic pathways that had not been previously associated with psoriasis risk such as retinol metabolism (Pcombined = 1.84 × 10(-4)), the transport of inorganic ions and amino acids (Pcombined = 1.57 × 10(-7)), and post-translational protein modification (Pcombined = 1.57 × 10(-7)). In the latter pathway, MGAT5 showed a strong network centrality, and its association with psoriasis risk was further validated in an additional case-control cohort of 3,429 individuals (P psoriasis susceptibility.

  15. Exergetical Evaluation of Biobased Synthesis Pathways

    Directory of Open Access Journals (Sweden)

    Philipp Frenzel

    2014-01-01

    Full Text Available The vast majority of today’s chemical products are based on crude oil. An attractive and sustainable alternative feedstock is biomass. Since crude oil and biomass differ in various properties, new synthesis pathways and processes have to be developed. In order to prioritize limited resources for research and development (R & D, their economic potential must be estimated in the early stages of development. A suitable measure for an estimation of the economic potential is based on exergy balances. Different structures of synthesis pathways characterised by the chemical exergy of the main components are evaluated. Based on a detailed evaluation of the underlying processes, general recommendations for future bio-based synthesis pathways are derived.

  16. Lectin Complement Pathway Proteins in Healthy Individuals

    DEFF Research Database (Denmark)

    Troldborg, Anne; Hansen, Annette; Hansen, Søren W K

    2017-01-01

    Since the discovery of the lectin pathway of complement activation, numerous clinical cohorts have been examined for one or more of the proteins, with the intention of uncovering the functions of the proteins or with the aim of discovering new biomarkers or diagnostic tools. To unveil the abnormal......, it is pivotal to know the normal. Our aim was to describe the concentrations of the eleven known proteins of the lectin pathway in serum and plasma and to uncover possible gender differences, age and diurnal variations, which must be taken into account for investigations in different cohorts. We examined...... the concentrations of all lectin pathway proteins (mannan-binding lectin (MBL), H-ficolin, L-ficolin, M-ficolin, collectin-K1, collectin-L1, MBL-associated serine protease 2 (MASP-2), MASP-3, MBL associated protein of 44 kDa (MAp44) and MAp19 in 300 Danish blood donors in serum and EDTA plasma in established assays...

  17. The Lectin Pathway of Complement and Biocompatibility

    DEFF Research Database (Denmark)

    Hein, Estrid; Garred, Peter

    2015-01-01

    In modern health technologies the use of biomaterials in the form of stents, haemodialysis tubes, artificial implants, bypass circuits etc. is rapidly expanding. The exposure of synthetic, foreign surfaces to the blood and tissue of the host, calls for strict biocompatibility in respect to contac...... been broadly documented. However, the specific role of lectin pathway and the pattern recognition molecules initiating the pathway has only been transiently investigated. Here we review the current data on the field....... activation, the coagulation system and the complement system. The complement system is an important part of the initial immune response and consists of fluid phase molecules in the blood stream. Three different activation pathways can initiate the complement system, the lectin, the classical...

  18. Policy Pathways: Energy Management Programmes for Industry

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2012-09-06

    The IEA Policy Pathway publications provide details on how to implement specific recommendations drawn from the IEA 25 Energy Efficiency Policy Recommendations. This Policy Pathway, jointly produced by the International Energy Agency and the Institute for Industrial Productivity, develops the critical steps for policy makers implementing energy management programmes for industry. Optimising energy use in industry is essential to improve industrial competitiveness and achieve wider societal goals such as energy security, economic recovery and development, climate change mitigation and environmental protection.While there is significant potential to decrease energy consumption in this sector, opportunities to improve energy efficiency are still under-exploited. Energy management programmes have shown to be instrumental in addressing many of the barriers that inhibit wide-scale uptake of energy management in industry. The Policy Pathway builds on lessons learned from country experiences and provides actionable guidance on how to plan and design, implement, evaluate and monitor energy management programmes for industry.

  19. Roles of RUNX in Hippo Pathway Signaling.

    Science.gov (United States)

    Passaniti, Antonino; Brusgard, Jessica L; Qiao, Yiting; Sudol, Marius; Finch-Edmondson, Megan

    2017-01-01

    The Runt-domain (RD) transcription factors (RUNX genes) are an important family of transcriptional mediators that interact with a variety of proteins including the Hippo pathway effector proteins, YAP and TAZ. In this chapter we focus on two examples of RUNX-TAZ/YAP interactions that have particular significance in human cancer. Specifically, recent evidence has found that RUNX2 cooperates with TAZ to promote epithelial to mesenchymal transition mediated by the soluble N-terminal ectodomain of E-Cadherin, sE-Cad. Contrastingly, in gastric cancer, RUNX3 acts as a tumor suppressor via inhibition of the YAP-TEAD complex and disruption of downstream YAP-mediated gene transcription and the oncogenic phenotype. The reports highlighted in this chapter add to the growing repertoire of instances of Hippo pathway crosstalk that have been identified in cancer. Elucidation of these increasingly complex interactions may help to identify novel strategies to target Hippo pathway dysregulation in human cancer.

  20. NOTCH pathway inactivation promotes bladder cancer progression.

    Science.gov (United States)

    Maraver, Antonio; Fernandez-Marcos, Pablo J; Cash, Timothy P; Mendez-Pertuz, Marinela; Dueñas, Marta; Maietta, Paolo; Martinelli, Paola; Muñoz-Martin, Maribel; Martínez-Fernández, Mónica; Cañamero, Marta; Roncador, Giovanna; Martinez-Torrecuadrada, Jorge L; Grivas, Dimitrios; de la Pompa, Jose Luis; Valencia, Alfonso; Paramio, Jesús M; Real, Francisco X; Serrano, Manuel

    2015-02-01

    NOTCH signaling suppresses tumor growth and proliferation in several types of stratified epithelia. Here, we show that missense mutations in NOTCH1 and NOTCH2 found in human bladder cancers result in loss of function. In murine models, genetic ablation of the NOTCH pathway accelerated bladder tumorigenesis and promoted the formation of squamous cell carcinomas, with areas of mesenchymal features. Using bladder cancer cells, we determined that the NOTCH pathway stabilizes the epithelial phenotype through its effector HES1 and, consequently, loss of NOTCH activity favors the process of epithelial-mesenchymal transition. Evaluation of human bladder cancer samples revealed that tumors with low levels of HES1 present mesenchymal features and are more aggressive. Together, our results indicate that NOTCH serves as a tumor suppressor in the bladder and that loss of this pathway promotes mesenchymal and invasive features.

  1. Research Resources for Nuclear Receptor Signaling Pathways.

    Science.gov (United States)

    McKenna, Neil J

    2016-08-01

    Nuclear receptor (NR) signaling pathways impact cellular function in a broad variety of tissues in both normal physiology and disease states. The complex tissue-specific biology of these pathways is an enduring impediment to the development of clinical NR small-molecule modulators that combine therapeutically desirable effects in specific target tissues with suppression of off-target effects in other tissues. Supporting the important primary research in this area is a variety of web-based resources that assist researchers in gaining an appreciation of the molecular determinants of the pharmacology of a NR pathway in a given tissue. In this study, selected representative examples of these tools are reviewed, along with discussions on how current and future generations of tools might optimally adapt to the future of NR signaling research. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  2. Amino Acid Biosynthesis Pathways in Diatoms

    Directory of Open Access Journals (Sweden)

    Mariusz A. Bromke

    2013-04-01

    Full Text Available Amino acids are not only building blocks for proteins but serve as precursors for the synthesis of many metabolites with multiple functions in growth and other biological processes of a living organism. The biosynthesis of amino acids is tightly connected with central carbon, nitrogen and sulfur metabolism. Recent publication of genome sequences for two diatoms Thalassiosira pseudonana and Phaeodactylum tricornutum created an opportunity for extensive studies on the structure of these metabolic pathways. Based on sequence homology found in the analyzed diatomal genes, the biosynthesis of amino acids in diatoms seems to be similar to higher plants. However, one of the most striking differences between the pathways in plants and in diatomas is that the latter possess and utilize the urea cycle. It serves as an important anaplerotic pathway for carbon fixation into amino acids and other N-containing compounds, which are essential for diatom growth and contribute to their high productivity.

  3. JNK pathway:diseases and therapeutic potential

    Institute of Scientific and Technical Information of China (English)

    Jie CUI; Ming ZHANG; Yong-qing ZHANG; Zhi-heng XU

    2007-01-01

    c-Jun N-terminal protein kinases (JNK), also known as stress-activated protein kinases, were originally identified by their ability to phosphorylate the N-terminal of the transcription factor c-Jun and by their activation in response to a variety of stresses. JNK are multifunctional kinases involved in many physiological processes. The JNK pathway has been shown to play a major role in apoptosis in many cell death paradigms and its association with a variety of pathological pro-cesses is gradually been recognized. This review will concentrate on describing the involvement of the JNK pathway in the context of different diseases and the potential to adopt the JNK pathway components as therapeutic targets.

  4. Targeting Specific Immunologic Pathways in Crohn's Disease.

    Science.gov (United States)

    Ramos, Guilherme Piovezani; Faubion, William A; Papadakis, Konstantinos A

    2017-09-01

    Understanding the immunologic pathways in intestinal inflammation is crucial for the development of new therapies that can maximize patient response and minimize toxicity. Targeting integrins and cytokines is intended to control leukocyte migration to effector sites or inhibit the action of proinflammatory cytokines. New approaches to preventing leukocyte migration may target integrin receptors expressed on the intestinal vascular endothelium. The interleukin (IL)-12/IL-23 pathway has been a therapeutic target of interest in controlling active Crohn's disease (CD). New therapeutic approaches in CD may involve the enhancement of anti-inflammatory cytokine pathways and modulation of cellular responses and intranuclear signals associated with intestinal inflammation. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Understanding trade pathways to target biosecurity surveillance

    Directory of Open Access Journals (Sweden)

    Manuel Colunga-Garcia

    2013-09-01

    Full Text Available Increasing trends in global trade make it extremely difficult to prevent the entry of all potential invasive species (IS. Establishing early detection strategies thus becomes an important part of the continuum used to reduce the introduction of invasive species. One part necessary to ensure the success of these strategies is the determination of priority survey areas based on invasion pressure. We used a pathway-centred conceptual model of pest invasion to address these questions: what role does global trade play in invasion pressure of plant ecosystems and how could an understanding of this role be used to enhance early detection strategies? We concluded that the relative level of invasion pressure for destination ecosystems can be influenced by the intensity of pathway usage (import volume and frequency, the number and type of pathways with a similar destination, and the number of different ecological regions that serve as the source for imports to the same destination. As these factors increase, pressure typically intensifies because of increasing a propagule pressure, b likelihood of transporting pests with higher intrinsic invasion potential, and c likelihood of transporting pests into ecosystems with higher invasibility. We used maritime containerized imports of live plants into the contiguous U.S. as a case study to illustrate the practical implications of the model to determine hotspot areas of relative invasion pressure for agricultural and forest ecosystems (two ecosystems with high potential invasibility. Our results illustrated the importance of how a pathway-centred model could be used to highlight potential target areas for early detection strategies for IS. Many of the hotspots in agricultural and forest ecosystems were within major U.S. metropolitan areas. Invasion ecologists can utilize pathway-centred conceptual models to a better understand the role of human-mediated pathways in pest establishment, b enhance current

  6. КОНЦЕПЦІЯ АНТРОПОЦЕНТРИЗМУ В НЕКЛАСИЧНІЙ ФІЛОСОФІЇ / The concept of anthropocentrism in the non-classical philosophy

    Directory of Open Access Journals (Sweden)

    Скакун Ігор

    2015-09-01

    Full Text Available Скакун Игорь. Концепция антропоцентризма в неклассической философии. В работе исследуется мировоззренческий и методологический потенциал антропоцентризма и его реализация в динамике парадигм человекомерности научного знания. Раскрывается суть идеи человекомерности и принципа антропоцентризма, формы их актуализации в постклассической парадигме знания. Ключевые слова: антропологизация, антропоцентризм, человек, методология, научная картина мира. Skakun Ihor. THE CONCEPT OF ANTHROPOCENTRISM IN THE NONCLASSICAL PHILOSOPHY. In the paper the ideological and methodological potential of anthropocentrism and its implementation in the dynamics of human dimensional paradigms of scientific knowledge is argued. The author reveals the essence of the idea of personality and principle of anthropocentrism, shapes their actualization in postclassical paradigms of knowledge. The concept of anthropocentrism became an independent philosophical concept, according to which man is the center and purpose of world creation. Anthropocentrism in non-classical philosophy outlined the importance of the qualitative change in the methodological approach of philosophical understanding of man. It should be emphasized that man-restructuring concept was only potential, as factors of its implementation (as it was in post-non-classical period to the just formed. Thinkers’ ideas of the transition period (from classic to non-classic and the ideas of thinkers formed a new era of post-non-classical objectivistic and subjectivist concepts of man. Awareness of the problem of man as the central

  7. Teaching Biochemical Pathways Using Concept Maps

    OpenAIRE

    Simon Brown

    2013-01-01

    The interesting paper by Dinarvand and Vaisi-Raygan (1) makes valuable points about a particularly challenging aspect of biochemistry learning and teaching. Their work prompts me to ask two questions and make a comment. First, what do the authors mean by a concept map (CM)? A pathway map could be considered a CM, but a CM could cover modes of regulation and kinetics in relation to particular reactions or pathways and there are many other possibilities. Irrespective of this, a CM can get extre...

  8. Supporting liver transplantation by clinical pathway intelligence.

    Science.gov (United States)

    Kirchner, K; Malessa, Ch; Herzberg, N; Krumnow, S; Habrecht, O; Scheuerlein, H; Bauschke, A; Settmacher, U

    2013-06-01

    A reproducible and transparent quality of clinical treatments plays an important role in the performance of a hospital. In liver transplantation (LT), this is particularly important for patient safety, resource planning, documentation, and quality management. Thus, the clinical pathway for LT was documented in an electronic format within our research project PIGE. Data from clinical information systems were linked to this pathway, which allows for process monitoring (the assessment of the current state for every patient in the LT process) and a retrospective analysis of all treatments in addition to all data pertaining to the treatment, for example, cost, time, number of personnel, etc.

  9. Pathways for scaling up public health interventions.

    Science.gov (United States)

    Indig, Devon; Lee, Karen; Grunseit, Anne; Milat, Andrew; Bauman, Adrian

    2017-08-01

    To achieve population-wide health improvement, public health interventions found effective in selected samples need to be 'scaled up' and implemented more widely. The pathways through which interventions are scaled up are not well characterised. The aim of this paper is to identify examples of public health interventions which have been scaled up and to develop a conceptual framework which quantifies and describes this process. A multi-stage international literature search was undertaken to identify examples of public health interventions in high income countries that have been scaled up or implemented at scale. Initial abstract review identified articles which met all the criteria of being a: 1) public health intervention; 2) chronic disease prevention focus; 3) program delivered at a wide geographical scale (state, national or international). Interventions were reviewed and coded into a conceptual framework pathway to document their scaling up process. For each program, an in-depth review of the identified articles was undertaken along with a broad internet based search to determine the outcomes of the dissemination process. A conceptual framework of scaling up pathways was developed that involved four stages (development, efficacy testing, real world trial and dissemination) to which the 40 programs were mapped. The search identified 40 public health interventions that showed evidence of being scaled up. Four pathways were identified to capture the different scaling up trajectories taken which included: 'Type I - Comprehensive' (55%) which passed through all four stages, 'Type II - Efficacy omitters' (5%) which did not conduct efficacy testing, 'Type III - Trial omitters' (25%) which did not conduct a real world trial, and 'Type IV - At scale dissemination' (15%) which skipped both efficacy testing and a real world trial. This is the first study to classify and quantify the potential pathways through which public health interventions in high income countries are

  10. PI3K pathway in NSCLC

    Directory of Open Access Journals (Sweden)

    Alex eMartínez Martí

    2012-01-01

    Full Text Available The phosphatidylinositol 3-kinases (PI3Ks are members of a family of intracellular lipid kinases that phosphorylate the 3’-hydroxyl group of phosphatidylinositol and phosphoinositides. PI3K regulate signaling pathways for neoplasia, including cell proliferation, adhesion, survival and motility. Different classes of PI3K have distinct roles in cellular signal transduction. PI3K pathway is activated by several different mechanisms in cancers, including, somatic mutation and gene amplification. In this review, we examine the literature addressing PI3K mutation status and gene amplification, with an emphasis on non-small cell lung cancer (NSCLC.

  11. Imaging neuronal pathways with 52Mn PET

    DEFF Research Database (Denmark)

    Napieczynska, Hanna; Severin, Gregory; Fonslet, Jesper

    2017-01-01

    tomography (PET) neuronal tract tracer. We used 52Mn for imaging dopaminergic pathways after a unilateral injection into the ventral tegmental area (VTA), as well as the striatonigral pathway after an injection into the dorsal striatum (STR) in rats. Furthermore, we tested potentially noxious effects...... of the radioactivity dose with a behavioral test and histological staining. 24 h after 52Mn administration, the neuronal tracts were clearly visible in PET images and statistical analysis confirmed the observed distribution of the tracer. We noticed a behavioral impairment in some animals treated with 170 kBq of 52Mn...... for PET imaging....

  12. Developmental pathways to antisocial behavior: the delayed-onset pathway in girls.

    Science.gov (United States)

    Silverthorn, P; Frick, P J

    1999-01-01

    Recent research has suggested that there are two distinct trajectories for the development of antisocial behavior in boys: a childhood-onset pathway and an adolescent-onset pathway. After reviewing the limited available research on antisocial girls, we propose that this influential method of conceptualizing the development of severe antisocial behavior may not apply to girls without some important modifications. Antisocial girls appear to show many of the correlates that have been associated with the childhood-onset pathway in boys, and they tend to show impaired adult adjustment, which is also similar to boys in the childhood-onset pathway. However, antisocial girls typically show an adolescent-onset to their antisocial behavior. We have proposed that these girls show a third developmental pathway which we have labeled the "delayed-onset" pathway. This model rests on the assumption that many of the putative pathogenic mechanisms that contribute to the development of antisocial behavior in girls, such as cognitive and neuropsychological deficits, a dysfunctional family environment, and/or the presence of a callous and unemotional interpersonal style, may be present in childhood, but they do not lead to severe and overt antisocial behavior until adolescence. Therefore, we propose that the delayed-onset pathway for girls is analogous to the childhood-onset pathway in boys and that there is no analogous pathway in girls to the adolescent-onset pathway in boys. Although this model clearly needs to be tested in future research, it highlights the need to test the applicability of current theoretical models for explaining the development of antisocial behavior in girls.

  13. Evolution of Ras-like GTPase signaling pathways

    NARCIS (Netherlands)

    van Dam, T.J.P.

    2011-01-01

    Signalling pathways are networks of interacting proteins that measure and integrate internal and external stimuli and regulate critical cellular processes accordingly. In these pathways intricate feedback loops are often observed and as a result signalling pathways are very complex. Pathways did not

  14. Discovery of Host Factors and Pathways Utilized in Hantaviral Infection

    Science.gov (United States)

    2015-09-01

    cellular pathways, and broadly effective inhibitors targeting these pathways, that impact numerous hantaviruses. In the longer run , we hypothesize...common cellular pathways, and broadly effective inhibitors targeting these pathways, that impact numerous hantaviruses. In the longer run , we...the Venus fluorescent protein via an internal ribosome entry site. The sequence and orientation of the insert was verified by complete sequencing

  15. Hippo pathway in mammary gland development and breast cancer.

    Science.gov (United States)

    Shi, Peiguo; Feng, Jing; Chen, Ceshi

    2015-01-01

    Accumulated evidence suggests that the Hippo signaling pathway plays crucial roles in mammary gland development and breast cancer. Key components of the Hippo pathway regulate breast epithelial cell proliferation, migration, invasion, and stemness. Additionally, the Hippo pathway regulates breast tumor growth, metastasis, and drug resistance. It is expected that the Hippo pathway will provide novel therapeutic targets for breast cancer. This review will discuss and summarize the roles of several core components of the Hippo pathway in mammary gland development and breast cancer.

  16. Nitric oxide-sensitive guanylyl cyclase is differentially regulated by nuclear and non-nuclear estrogen pathways in anterior pituitary gland.

    Directory of Open Access Journals (Sweden)

    Jimena P Cabilla

    Full Text Available 17β-estradiol (E2 regulates hormonal release as well as proliferation and cell death in the pituitary. The main nitric oxide receptor, nitric oxide sensitive- or soluble guanylyl cyclase (sGC, is a heterodimer composed of two subunits, α and β, that catalyses cGMP formation. α1β1 is the most abundant and widely expressed heterodimer, showing the greater activity. Previously we have shown that E2 decreased sGC activity but exerts opposite effects on sGC subunits increasing α1 and decreasing β1 mRNA and protein levels. In the present work we investigate the mechanisms by which E2 differentially regulates sGC subunits' expression on rat anterior pituitary gland. Experiments were performed on primary cultures of anterior pituitary cells from adult female Wistar rats at random stages of estrous cycle. After 6 h of E2 treatment, α1 mRNA and protein expression is increased while β1 levels are down-regulated. E2 effects on sGC expression are partially dependent on de novo transcription while de novo translation is fully required. E2 treatment decreased HuR mRNA stabilization factor and increased AUF1 p37 mRNA destabilization factor. E2-elicited β1 mRNA decrease correlates with a mRNA destabilization environment in the anterior pituitary gland. On the other hand, after 6 h of treatment, E2-BSA (1 nM and E2-dendrimer conjugate (EDC, 1 nM were unable to modify α1 or β1 mRNA levels, showing that nuclear receptor is involved in E2 actions. However, at earlier times (3 h, 1 nM EDC causes a transient decrease of α1 in a PI3k-dependent fashion. Our results show for the first time that E2 is able to exert opposite actions in the anterior pituitary gland, depending on the activation of classical or non-classical pathways. Thus, E2 can also modify sGC expression through membrane-initiated signals bringing to light a new point of regulation in NO/sGC pathway.

  17. PathwayExplorer: web service for visualizing high-throughput expression data on biological pathways.

    Science.gov (United States)

    Mlecnik, Bernhard; Scheideler, Marcel; Hackl, Hubert; Hartler, Jürgen; Sanchez-Cabo, Fatima; Trajanoski, Zlatko

    2005-07-01

    While generation of high-throughput expression data is becoming routine, the fast, easy, and systematic presentation and analysis of these data in a biological context is still an obstacle. To address this need, we have developed PathwayExplorer, which maps expression profiles of genes or proteins simultaneously onto major, currently available regulatory, metabolic and cellular pathways from KEGG, BioCarta and GenMAPP. PathwayExplorer is a platform-independent web server application with an optional standalone Java application using a SOAP (simple object access protocol) interface. Mapped pathways are ranked for the easy selection of the pathway of interest, displaying all available genes of this pathway with their expression profiles in a selectable and intuitive color code. Pathway maps produced can be downloaded as PNG, JPG or as high-resolution vector graphics SVG. The web service is freely available at https://pathwayexplorer.genome.tugraz.at; the standalone client can be downloaded at http://genome.tugraz.at.

  18. Pathway Tools version 19.0 update: software for pathway/genome informatics and systems biology.

    Science.gov (United States)

    Karp, Peter D; Latendresse, Mario; Paley, Suzanne M; Krummenacker, Markus; Ong, Quang D; Billington, Richard; Kothari, Anamika; Weaver, Daniel; Lee, Thomas; Subhraveti, Pallavi; Spaulding, Aaron; Fulcher, Carol; Keseler, Ingrid M; Caspi, Ron

    2016-09-01

    Pathway Tools is a bioinformatics software environment with a broad set of capabilities. The software provides genome-informatics tools such as a genome browser, sequence alignments, a genome-variant analyzer and comparative-genomics operations. It offers metabolic-informatics tools, such as metabolic reconstruction, quantitative metabolic modeling, prediction of reaction atom mappings and metabolic route search. Pathway Tools also provides regulatory-informatics tools, such as the ability to represent and visualize a wide range of regulatory interactions. This article outlines the advances in Pathway Tools in the past 5 years. Major additions include components for metabolic modeling, metabolic route search, computation of atom mappings and estimation of compound Gibbs free energies of formation; addition of editors for signaling pathways, for genome sequences and for cellular architecture; storage of gene essentiality data and phenotype data; display of multiple alignments, and of signaling and electron-transport pathways; and development of Python and web-services application programming interfaces. Scientists around the world have created more than 9800 Pathway/Genome Databases by using Pathway Tools, many of which are curated databases for important model organisms.

  19. Robust de novo pathway enrichment with KeyPathwayMiner 5

    DEFF Research Database (Denmark)

    Alcaraz, Nicolas; List, Markus; Dissing-Hansen, Martin;

    2016-01-01

    Identifying functional modules or novel active pathways, recently termed de novo pathway enrichment, is a computational systems biology challenge that has gained much attention during the last decade. Given a large biological interaction network, KeyPathwayMiner extracts connected subnetworks tha...... several network perturbation techniques and over a range of perturbation degrees. In addition, users may now provide a gold-standard set to determine how enriched extracted pathways are with relevant genes compared to randomized versions of the original network.......Identifying functional modules or novel active pathways, recently termed de novo pathway enrichment, is a computational systems biology challenge that has gained much attention during the last decade. Given a large biological interaction network, KeyPathwayMiner extracts connected subnetworks...... that are enriched for differentially active entities from a series of molecular profiles encoded as binary indicator matrices. Since interaction networks constantly evolve, an important question is how robust the extracted results are when the network is modified. We enable users to study this effect through...

  20. Targeting stem cell signaling pathways for drug discovery: advances in the Notch and Wnt pathways.

    Science.gov (United States)

    An, Songzhu Michael; Ding, Qiang; Zhang, Jie; Xie, JingYi; Li, LingSong

    2014-06-01

    Signaling pathways transduce extracellular stimuli into cells through molecular cascades to regulate cellular functions. In stem cells, a small number of pathways, notably those of TGF-β/BMP, Hedgehog, Notch, and Wnt, are responsible for the regulation of pluripotency and differentiation. During embryonic development, these pathways govern cell fate specifications as well as the formation of tissues and organs. In adulthood, their normal functions are important for tissue homeostasis and regeneration, whereas aberrations result in diseases, such as cancer and degenerative disorders. In complex biological systems, stem cell signaling pathways work in concert as a network and exhibit crosstalk, such as the negative crosstalk between Wnt and Notch. Over the past decade, genetic and genomic studies have identified a number of potential drug targets that are involved in stem cell signaling pathways. Indeed, discovery of new targets and drugs for these pathways has become one of the most active areas in both the research community and pharmaceutical industry. Remarkable progress has been made and several promising drug candidates have entered into clinical trials. This review focuses on recent advances in the discovery of novel drugs which target the Notch and Wnt pathways.

  1. Crowding in the S-cone pathway.

    Science.gov (United States)

    Coates, Daniel R; Chung, Susana T L

    2016-05-01

    The spatial extent of interference from nearby object or contours (the critical spacing of "crowding") has been thoroughly characterized across the visual field, typically using high contrast achromatic stimuli. However, attempts to link this measure with known properties of physiological pathways have been inconclusive. The S-cone pathway, with its ease of psychophysical isolation and known anatomical characteristics, offers a unique tool to gain additional insights into crowding. In this study, we measured the spatial extent of crowding in the S-cone pathway at several retinal locations using a chromatic adaptation paradigm. S-cone crowding was evident and extensive, but its spatial extent changed less markedly as a function of retinal eccentricity than the extent found using traditional achromatic stimuli. However, the spatial extent agreed with that of low contrast achromatic stimuli matched for isolated resolvability. This suggests that common cortical mechanisms mediate the crowding effect in the S-cone and achromatic pathway, but contrast is an important factor. The low contrast of S-cone stimuli makes S-cone vision more acuity-limited than crowding-limited.

  2. Exergetical evaluation of biobased synthesis pathways

    NARCIS (Netherlands)

    Frenzel, P.; Hillerbrand, R.; Pfennig, A.

    2014-01-01

    The vast majority of today’s chemical products are based on crude oil. An attractive and sustainable alternative feedstock is biomass. Since crude oil and biomass differ in various properties, new synthesis pathways and processes have to be developed. In order to prioritize limited resources for res

  3. Pathways to deep decarbonization in India

    DEFF Research Database (Denmark)

    Shukla, P.; Dhar, Subash; Pathak, Minal

    This report is a part of the global Deep Decarbonisation Pathways (DDP) Project. The analysis consider two development scenarios for India and assess alternate roadmaps for transiting to a low carbon economy consistent with the globally agreed 2°C stabilization target. The report does not consider...

  4. Salicylic acid-independent plant defence pathways

    NARCIS (Netherlands)

    Pieterse, C.M.J.; Loon, L.C. van

    1999-01-01

    Salicylic acid is an important signalling molecule involved in both locally and systemically induced disease resistance responses. Recent advances in our understanding of plant defence signalling have revealed that plants employ a network of signal transduction pathways, some of which are independen

  5. Pathways to Authenticity in Operatic Interpretation

    DEFF Research Database (Denmark)

    Grund, Cynthia M.; Westney, WIlliam

    through physically interactive and expressive warm-up exercises that break down barriers at the start of the session, and through interactive and experimental techniques in response to the performances themselves. On this approach, physicality and interactivity provide pathways to authenticity on the part...

  6. The Student Affairs Pathway to the Presidency

    Science.gov (United States)

    Putman, Jeffrey Scott

    2011-01-01

    The purpose of this study is to determine the pathway issues supporting or challenging the advancement of student affairs officers to college and university presidencies and the experiences and skills student affairs officers must have to be competitive candidates in searches for presidencies. There is an impending serious gap between the number…

  7. Use of pathway information in molecular epidemiology

    Directory of Open Access Journals (Sweden)

    Thomas Duncan C

    2009-10-01

    Full Text Available Abstract Candidate gene studies are generally motivated by some form of pathway reasoning in the selection of genes to be studied, but seldom has the logic of the approach been carried through to the analysis. Marginal effects of polymorphisms in the selected genes, and occasionally pairwise gene-gene or gene-environment interactions, are often presented, but a unified approach to modelling the entire pathway has been lacking. In this review, a variety of approaches to this problem is considered, focusing on hypothesis-driven rather than purely exploratory methods. Empirical modelling strategies are based on hierarchical models that allow prior knowledge about the structure of the pathway and the various reactions to be included as 'prior covariates'. By contrast, mechanistic models aim to describe the reactions through a system of differential equations with rate parameters that can vary between individuals, based on their genotypes. Some ways of combining the two approaches are suggested and Bayesian model averaging methods for dealing with uncertainty about the true model form in either framework is discussed. Biomarker measurements can be incorporated into such analyses, and two-phase sampling designs stratified on some combination of disease, genes and exposures can be an efficient way of obtaining data that would be too expensive or difficult to obtain on a full candidate gene sample. The review concludes with some thoughts about potential uses of pathways in genome-wide association studies.

  8. Signaling pathways regulating murine pancreatic development

    DEFF Research Database (Denmark)

    Serup, Palle

    2012-01-01

    The recent decades have seen a huge expansion in our knowledge about pancreatic development. Numerous lineage-restricted transcription factor genes have been identified and much has been learned about their function. Similarly, numerous signaling pathways important for pancreas development have...

  9. Final report on the Pathway Analysis Task

    Energy Technology Data Exchange (ETDEWEB)

    Whicker, F.W.; Kirchner, T.B. [Colorado State Univ., Fort Collins, CO (United States)

    1993-04-01

    The Pathway Analysis Task constituted one of several multi-laboratory efforts to estimate radiation doses to people, considering all important pathways of exposure, from the testing of nuclear devices at the Nevada Test Site (NTS). The primary goal of the Pathway Analysis Task was to predict radionuclide ingestion by residents of Utah, Nevada, and portions of seven other adjoining western states following radioactive fallout deposition from individual events at the NTS. This report provides comprehensive documentation of the activities and accomplishments of Colorado State University`s Pathway Analysis Task during the entire period of support (1979--91). The history of the project will be summarized, indicating the principal dates and milestones, personnel involved, subcontractors, and budget information. Accomplishments, both primary and auxiliary, will be summarized with general results rather than technical details being emphasized. This will also serve as a guide to the reports and open literature publications produced, where the methodological details and specific results are documented. Selected examples of results on internal dose estimates are provided in this report because the data have not been published elsewhere.

  10. Vitamins and aging: pathways to NAD+ synthesis.

    Science.gov (United States)

    Denu, John M

    2007-05-04

    Recent genetic evidence reveals additional salvage pathways for NAD(+) synthesis. In this issue, Belenky et al. (2007) report that nicotinamide riboside, a new NAD(+) precursor, regulates Sir2 deacetylase activity and life span in yeast. The ability of nicotinamide riboside to enhance life span does not depend on calorie restriction.

  11. Whole Algae Hydrothermal Liquefaction Technology Pathway

    Energy Technology Data Exchange (ETDEWEB)

    Biddy, M.; Davis, R.; Jones, S.

    2013-03-01

    This technology pathway case investigates the feasibility of using whole wet microalgae as a feedstock for conversion via hydrothermal liquefaction. Technical barriers and key research needs have been assessed in order for the hydrothermal liquefaction of microalgae to be competitive with petroleum-derived gasoline-, diesel-, and jet-range hydrocarbon blendstocks.

  12. Syngas Upgrading to Hydrocarbon Fuels Technology Pathway

    Energy Technology Data Exchange (ETDEWEB)

    Talmadge, M.; Biddy, Mary J.; Dutta, Abhijit; Jones, Susanne B.; Meyer, Pimphan A.

    2013-03-31

    In support of the Bioenergy Technologies Office, the National Renewable Energy Laboratory (NREL) and the Pacific Northwest National Laboratory (PNNL) are undertaking studies of biomass conversion technologies to hydrocarbon fuels to identify barriers and target research toward reducing conversion costs. Process designs and preliminary economic estimates for each of these pathway cases were developed using rigorous modeling tools (Aspen Plus and Chemcad). These analyses incorporated the best information available at the time of development, including data from recent pilot and bench-scale demonstrations, collaborative industrial and academic partners, and published literature and patents. This pathway case investigates the upgrading of biomass derived synthesis gas (‘syngas’) to hydrocarbon biofuels. While this specific discussion focuses on the conversion of syngas via a methanol intermediate to hydrocarbon blendstocks, there are a number of alternative conversion routes for production of hydrocarbons through a wide array of intermediates from syngas. Future work will also consider the variations to this pathway to determine the most economically viable and risk adverse conversion route. Technical barriers and key research needs have been identified that should be pursued for the syngas to hydrocarbon pathway to be competitive with petroleum-derived gasoline, diesel and jet range blendstocks.

  13. Learning figurative idioms via cognitive semantic pathway

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    In FTL contexts, traditional view treats idiomatic language as essentially arbitrary, which has typically led to the belief that they can only be learned through blind memoriztion. However, the cognitive semantic idea considers that idioms are typically motivated, which can help learners to identify their senses. This paper demonstrates how to learn figurative idioms through cognitive semantic pathway by taking anger as one example.

  14. Oxidative stress: Biomarkers and novel therapeutic pathways.

    Science.gov (United States)

    Maiese, Kenneth; Chong, Zhao Zhong; Hou, Jinling; Shang, Yan Chen

    2010-03-01

    Oxidative stress significantly impacts multiple cellular pathways that can lead to the initiation and progression of varied disorders throughout the body. It therefore becomes imperative to elucidate the components and function of novel therapeutic strategies against oxidative stress to further clinical diagnosis and care. In particular, both the growth factor and cytokine erythropoietin (EPO) and members of the mammalian forkhead transcription factors of the O class (FoxOs) may offer the greatest promise for new treatment regimens since these agents and the cellular pathways they oversee cover a range of critical functions that directly influence progenitor cell development, cell survival and degeneration, metabolism, immune function, and cancer cell invasion. Furthermore, both EPO and FoxOs function not only as therapeutic targets, but also as biomarkers of disease onset and progression, since their cellular pathways are closely linked and overlap with several unique signal transduction pathways. However, biological outcome with EPO and FoxOs may sometimes be both unexpected and undesirable that can raise caution for these agents and warrant further investigations. Here we present the exciting as well as complicated role EPO and FoxOs possess to uncover the benefits as well as the risks of these agents for cell biology and clinical care in processes that range from stem cell development to uncontrolled cellular proliferation.

  15. Pathway Analysis: State of the Art

    Science.gov (United States)

    García-Campos, Miguel A.; Espinal-Enríquez, Jesús; Hernández-Lemus, Enrique

    2015-01-01

    Pathway analysis is a set of widely used tools for research in life sciences intended to give meaning to high-throughput biological data. The methodology of these tools settles in the gathering and usage of knowledge that comprise biomolecular functioning, coupled with statistical testing and other algorithms. Despite their wide employment, pathway analysis foundations and overall background may not be fully understood, leading to misinterpretation of analysis results. This review attempts to comprise the fundamental knowledge to take into consideration when using pathway analysis as a hypothesis generation tool. We discuss the key elements that are part of these methodologies, their capabilities and current deficiencies. We also present an overview of current and all-time popular methods, highlighting different classes across them. In doing so, we show the exploding diversity of methods that pathway analysis encompasses, point out commonly overlooked caveats, and direct attention to a potential new class of methods that attempt to zoom the analysis scope to the sample scale. PMID:26733877

  16. Signaling pathways regulating murine pancreatic development

    DEFF Research Database (Denmark)

    Serup, Palle

    2012-01-01

    The recent decades have seen a huge expansion in our knowledge about pancreatic development. Numerous lineage-restricted transcription factor genes have been identified and much has been learned about their function. Similarly, numerous signaling pathways important for pancreas development have...

  17. Novel inositol catabolic pathway in Thermotoga maritima.

    Science.gov (United States)

    Rodionova, Irina A; Leyn, Semen A; Burkart, Michael D; Boucher, Nathalie; Noll, Kenneth M; Osterman, Andrei L; Rodionov, Dmitry A

    2013-08-01

    myo-inositol (MI) is a key sugar alcohol component of various metabolites, e.g. phosphatidylinositol-based phospholipids that are abundant in animal and plant cells. The seven-step pathway of MI degradation was previously characterized in various soil bacteria including Bacillus subtilis. Through a combination of bioinformatics and experimental techniques we identified a novel variant of the MI catabolic pathway in the marine hyperthermophilic bacterium Thermotoga maritima. By using in vitro biochemical assays with purified recombinant proteins we characterized four inositol catabolic enzymes encoded in the TM0412-TM0416 chromosomal gene cluster. The novel catabolic pathway in T. maritima starts as the conventional route using the myo-inositol dehydrogenase IolG followed by three novel reactions. The first 2-keto-myo-inositol intermediate is oxidized by another, previously unknown NAD-dependent dehydrogenase TM0412 (named IolM), and a yet unidentified product of this reaction is further hydrolysed by TM0413 (IolN) to form 5-keto-l-gluconate. The fourth step involves epimerization of 5-keto-l-gluconate to d-tagaturonate by TM0416 (IolO). T. maritima is unable to grow on myo-inositol as a single carbon source. The determined in vitro specificity of the InoEFGK (TM0418-TM0421) transporter to myo-inositol-phosphate suggests that the novel pathway in Thermotoga utilizes a phosphorylated derivative of inositol.

  18. Fetal and neonatal pathways to obesity.

    Science.gov (United States)

    Gluckman, Peter D; Hanson, Mark A; Beedle, Alan S; Raubenheimer, David

    2008-01-01

    Evolutionary and developmental perspectives add considerably to our understanding of the aetiology of obesity and its related disorders. One pathway to obesity represents the maladaptive consequences of an evolutionarily preserved mechanism by which the developing mammal monitors nutritional cues from its mother and adjusts its developmental trajectory accordingly. Prediction of a nutritionally sparse environment leads to a phenotype that promotes metabolic parsimony by favouring fat deposition, insulin resistance, sarcopenia and low energy expenditure. But this adaptive mechanism evolved to accommodate gradual changes in nutritional environment; rapid transition to a situation of high energy density results in a mismatch between predicted and actual environments and increased susceptibility to metabolic disease. This pathway may also explain why breast and bottle feeding confer different risks of obesity. We discuss how early environmental signals act through epigenetic mechanisms to alter metabolic partitioning, glucocorticoid action and neuroendocrine control of appetite. A second pathway involves alterations in fetal insulin levels, as seen in gestational diabetes, leading to increased prenatal fat mass which is subsequently amplified by postnatal factors. Both classes of pathway may coexist in an individual. This developmental approach to obesity suggests that potential interventions will vary according to the target population.

  19. Notch pathway is dispensable for adipocyte specification.

    Science.gov (United States)

    Nichols, Amy M; Pan, Yonghua; Herreman, An; Hadland, Brandon K; De Strooper, Bart; Kopan, Raphael; Huppert, Stacey S

    2004-09-01

    In the past decade we have witnessed an epidemic of obesity in developed countries. Therefore, understanding the mechanisms involved in regulation of body weight is becoming an increasingly important goal shared by the public and the scientific community. The key to fat deposition is the adipocyte, a specialized cell that plays a critical role in energy balance and appetite regulation. Much of our knowledge of adipogenesis comes from studies using preadipocytic cell lines that have provided important information regarding molecular control of adipocyte differentiation. However, they fall short of revealing how naive cells acquire competence for adipogenesis. Studies in preadipocytes indicate that the Notch pathway plays a role in regulating adipogenesis (Garces et al.: J Biol Chem 272:29729-29734, 1997). Given the known biological functions of Notch in mediating cell fate decisions (Artavanis-Tsakonas et al.: Science 284:770-776, 1999), we wished to test the hypothesis that the Notch pathway is required for this cellular program by examining adipogenesis in several genetic loss-of-function models that encompass the entire pathway. We conclude that the "canonical" Notch signaling pathway is dispensable for adipocyte specification and differentiation from either mesenchymal or epithelial progenitors.

  20. Students' Perspectives of an EAP Pathway Program

    Science.gov (United States)

    Dooey, Patricia

    2010-01-01

    Increasing numbers of overseas students are applying to study at universities in Australia. Many students who meet all of the university's academic entry requirements except English language proficiency are offered pathway programs which prepare them for their tertiary studies. To date, much of the research relating to international students…